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病理病態学腫瘍病理学/神経機能病理学(病理学第二)

研究室概要

旧病理学第2講座は昭和14年、名古屋帝国大学の創立に伴って設置された。
初代教授の大島福造は発癌ウィルスによる家鶏肉腫の発生の研究をライフワークとした。この研究はその後の発癌遺伝子研究につながる内容を含んだ先駆的な研究であった。
昭和33年に教授に就任した田内久は、肺癌の研究、老化の研究などに多大な業績をあげた。
昭和53年には星野宗光が教授に就任し、癌の電子顕微鏡的研究、マウス乳癌ウィルスの研究を行った。
平成元年に教授に就任した松山睦司は胸腺腫の研究をテーマとし、ユニークな胸腺腫発生ラットを用いた研究を行った。
平成8年には高橋雅英が教授に就任し、自らが発見したRET癌遺伝子を中心に癌関連遺伝子による発癌機構の解明や神経系の形成に関する研究を展開している。
教室からは婦人科腫瘍病理の故牛島宥(名大名誉教授)、乳腺病理の故田村潤(国立名古屋病院名誉院長)、早期胃癌研究の故長与健夫(愛知県がんセンター名誉総長)、糖鎖と癌転移研究の小島清秀(名大名誉教授)、癌と間質の研究の故竹内純(名大教授)、佐賀信介(愛知医大教授)、悪性リンパ腫研究の社本幹博(藤田保健衛生大学名誉教授)、ウィルス感染と発生異常の研究の筒井祥博(浜松医大名誉教授)、卵巣腫瘍病理の中島伸夫(名大名誉教授)などの人材が輩出している。
平成12年4月より大学院重点化により旧病理学第1講座と病理学第2講座は病理病態学講座として1つの大講座に再編された。旧病理学第2講座は専門分野として腫瘍病理学と神経機能病理学を担当することとなった。
現在の教室の主要テーマは発癌の分子メカニズムの解明と癌の新規診断法の開発、神経系の形成に関わる研究である。

研究プロジェクト

高橋が発見したRET遺伝子(Takahashi et al., Cell, 1985)をはじめとした受容体型チロシンキナーゼおよびその下流の細胞内シグナル伝達系を介した発癌および神経系の形成、腎臓の発生の分子メカニズムに関する研究を展開している。
特に、最近発見した癌遺伝子AKTの新規基質Girdinはアクチン結合蛋白であり、増殖因子刺激によって誘導される癌細胞、線維芽細胞、血管内皮細胞の運動に極めて重要な役割を果たしていることを明らかにし、注目を集めている(Enomoto et al., Developmental Cell, 2005; Kitamura et al., Nature Cell Biology, 2008)。
さらに、CD109というGPIアンカー型細胞表面蛋白がヒトの扁平上皮癌や特殊なタイプの乳癌に発現していることを明らかにし、その診断、治療法開発への応用研究を展開している(Hashimoto et al., Oncogene 2004; Hasegawa et al., Pathology Int., 2008)。
その他、RET Finger Protein (RFP)と名づけた核蛋白の細胞増殖における役割(Takahashi et al., Mol. Cell. Biol.; Shimono et al., J. Biol. Chem., 2000, 2003, 2005)、DNA修復遺伝子の機能に関する研究(Murakumo et al., J. Biol. Chem., 2001, Genes Cells, 2006)も行っている。 分子生物学、生化学、細胞生物学、病理形態学、発生工学(遺伝子組み換えマウス)といった多角的な手法を取り入れて研究活動を行っている。

  1. RET遺伝子の生理機能の解明と変異による疾患発症のメカニズム
    RETは多発性内分泌腫瘍症(Multiple Endocrine Neoplasia, MEN)2A型、MEN2B型、家族性甲状腺髄様癌(Familial Medullary Thyroid Carcinoma, FMTC)、Hirschsprung病といった複数の遺伝性疾患の原因遺伝子である。臨床像の全く異なる疾患が1つの遺伝子の変異の違いによって発症する点で注目されている。われわれの研究グループはRET遺伝子変異によるこれらの疾患の発症メカニズムについて世界に先駆けて解明してきた(Asai et al., Mol. Cell. Biol., 1995; Iwashita et al., Hum. Mol. Genet., 1996, Gastroenterology, 2001; Kawai et al., Cancer Res. 2000; Takahashi et al., Cytokine Growth Factor Review, 2001)。  1996年から97年にかけて米国Genentech社との共同研究によりRETのリガンドが神経栄養因子Glial Cell Line-Derived Neurotrophic Factor (GDNF)であることを明らかにした(Treanor, Nature 1996; Klein, Nature 1997)。GDNFはドーパミン作動性ニューロンに対する神経栄養因子として発見され、パーキンソン病の治療薬として期待されている。 さらに、GDNF-RETシグナル伝達系の腸管神経系形成における役割について、遺伝子組み換えマウスを用いて明らかにしてきた(Jijiwa et al., Mol. Cell. Biol. 2004; Asai et al., Development, 2006)。
  2. 癌蛋白AKTの新規基質Girdinの発見とその機能解析
    AKTは種々のヒト癌細胞において活性化され、浸潤・転移など癌細胞の悪性度を増強するということが報告されている。またAKTの活性化は線維芽細胞や白血球の運動能にも重要であるということが報告されていたが、そのメカニズムは明らかでなかった。われわれのグループは酵母two-hybrid法を用いてAKTの新規結合蛋白Girdinを同定し、その機能解析を行ったところアクチン結合蛋白であることを明らかにし、増殖因子刺激における線維芽細胞の運動に重要な役割を果たしていることを明らかにした(Enomoto et al., Developmental Cell., 2005)。(この遺伝子はほぼ同時期に複数のグループから、AKT phosphorylation enhancer (APE)、Galpha-interacting vesicle-associated protein (GIV)、Hook-related protein 1 (HkRP1)と報告された遺伝子と同一遺伝子であった)。  Girdinの発現は細胞運動の際、先導端に形成されるラメリポディアの形成に関与していることを明らかにし、癌細胞、血管内皮細胞の運動に関わることにより癌細胞の浸潤、転移や血管新生に重要な役割を果たしていることを証明した(Jiang et al., Cancer Res. 2008; Kitamura et. al., Nature Cell Biology, 2008)。現在、さらに胎生期の神経細胞の移動におけるGirdinの役割について解析を進めている。
  3. GPIアンカー型膜蛋白CD109の癌細胞のおける発現の意義と診断・治療への応用
    MEN2B型変異RET遺伝子により発現誘導される遺伝子をDifferential Display法により解析した結果、CD109遺伝子を同定した。CD109遺伝子の発現を種々の癌細胞にて検索したところ、肺、食道、子宮の扁平上皮癌で高発現を示すことを明らかにした(Hashimoto et al., Oncogene 2004; Sato et al., Pathology Int. 2007)。さらに乳癌細胞における発現を検索する過程で、乳癌の中で予後の悪いことが知られている基底細胞型乳癌において特異的に発現していることを見つけた(Hasegawa et al., Pathology Int., 2008)。これら癌細胞におけるCD109発現の意義や、診断・治療への応用について研究を進めている。

核蛋白RFPの機能解析と癌細胞における発現の意義
RET Finger Protein (RFP)はリングフィンガー構造を有する核蛋白であり、RETと融合蛋白を形成するころにより癌蛋白として活性化されることを明らかにしていた(Takahashi et al., Mol. Cell. Biol. 1987, 1988)。RFPは強力な転写抑制を有し、種々の核蛋白(EPC1, HDAC, Mi-2など)と相互作用することにより、その機能を発現していることを証明した(Shimono et al., J. Biol. Chem., 2000, 2003, 2005)。  RFPはすべての癌細胞株で高発現をしているので、現在RFPの発現が癌細胞にどのような生物学的特性を与えるか解析を進めている。

教員

構成員名役職所属
髙橋 雅英 教授 分子病理学
浅井 直也 准教授 分子病理学
榎本 篤 准教授 腫瘍病理学
三井 伸二 助教 分子病理学
翁 良 特任助教 腫瘍病理学
高岸 麻紀 特任助教 腫瘍病理学
白木 之浩 特任助教 腫瘍病理学

研究実績

  • 2015年
    1. Yamamura Y, Asai N, Enomoto A, Kato T, Mii S, Kondo Y, Ushida K., Niimi, K, Tsunoda N, Nagino M, Ichihara S, Furukawa K, Maeda K, Murohara T, Takahashi M.Akt-Girdin signaling in cancer-associated fibroblasts contributes to tumor progression.Cancer Res. 75: 813-823 (2015).
    2. Takashima S, Kanatsu-Shinohara M, Tanaka T, Morimoto H, Inoue K, Ogonuki N, Jijiwa M, Takahashi M, Ogura A, Shinohara T.Functional Differences between GDNF-Dependent and FGF2-Dependent Mouse Spermatogonial Stem Cell Self-Renewal.Stem Cell Rep. 4: 489-502 (2015).
    3. Mansour MA, Hyodo T, Ito S, Kurita K, Kokuryo T, Uehara K, Nagino M, Takahashi M, Hamaguchi M, Senga, T.SATB2 suppresses the progression of colorectal cancer cells via inactivation of MEK5/ERK5 signaling.FEBS J. 282: 1394-1405 (2015).
    4. Omori K, Asai M, Kuga D, Ushida K, Izuchi T, Mii S, Enomoto A, Asai N, Nagino M, Takahashi M.Girdin is phosphorylated on tyrosine 1798 when associated with structures required for migration.Biochem. Biophys. Res. Commun. 458: 934-940 (2015).
    5. Zhang J-M, Murakumo Y, Hagiwara S, Jiang P, Mii S, Kalyoncu E, Saito S, Suzuki C, Sakurai Y, Numata Y, Yamamoto T, Takahashi, M.CD109 attenuates TGFbeta1 signaling and enhances EGF signaling in SK-MG-1 human glioblastoma cells.Biochem. Biophys. Res. Commun. 459: 252-258 (2015).
    6. Noda T, Maeda K, Hayano S, Asai N, Enomoto A, Takahashi M, Murohara, T.A new ER stress regulator, Gipie, regulates the survival of vascular smooth muscle cells and the neointima formation after vascular injury.Arterioscler. Thromb. Vasc. Biol. 35: 1246-1253 (2015).
    7. Ichimiya H, Maeda K, Enomoto A, Weng L, Takahashi M, Murohara, T.Girdin/GIV regulates transendothelial permeability by controlling VE-cadherin trafficking through the small GTPase, R-Ras.Biochem. Biophys. Res. Commun. 461: 260-267 (2015).
    8. Iwama S, Sugimura Y, Kiyota A, Kato T, Enomoto A, Suzuki H, Iwata N, Takeuchi S, Nakashima K, Takagi H, Izumida H, Ochiai H, Fujisawa H, Suga H, Arima H, Shimoyama Y, Takahashi M, Nishioka H. Ishikawa SE, Shimatsu A, Caturegli P, Oiso Y.Rabphilin-3A as a Targeted Autoantigen in Lymphocytic Infundibulo-neurohypophysitisJ. Clin. Endocrinol .Metab. 100: E946-54 (2015).
    9. Muramatsu A, Enomoto A, Kato T, Weng L, Kuroda K, Asai N, Asai M, Mii S, Takahashi M.Potential involvement of kinesin-1 in the regulation of subcellular localization of Girdin.Biochem Biophys Res Commun. 463: 999-1005 (2015).
    10. Hayano S, Takefuji M, Maeda K, Noda T, Ichimiya H, Kobayashi K, Enomoto A, Asai N, Takahashi M, Murohara, T.Akt-dependent Girdin phosphorylation regulates repair processes after acute myocardial infarction.J Mol Cell Cardiol. 88: 55-63 (2015)
  • 2014年
    1. Nakai T, Nagai T, Tanaka M, Itoh N, Asai N, Enomoto A, Asai M, Yamada S, Saifullah AB, Sokabe M, Takahashi M, Yamada, K.Girdin phosphorylation is crucial for synaptic plasticity and memory: Potential role in the interaction of BDNF/TrkB/Akt signaling with NMDA receptor.J Neurosci. 34: 14995-15008 (2014).
    2. Weng L, Enomoto A, Miyoshi H, Takahashi K, Asai N, Morone N, Jiang P, An J, Kato T, Kuroda K, Watanabe T, Asai M, Ishida-Takagishi M, Murakumo Y, Nakashima H, Kaibuchi K, Takahashi M.Regulation of cargo-selective endocytosis by dynamin 2 GTPase-activating protein girdin.EMBO J. 33: 2098-2112 (2014).
    3. Ota H, Hikita T, Sawada M, Nishioka T, Matsumoto M, Komura M, Ohno A, Kamiya Y, Miyamoto T, Asai N, Enomoto A, Takahashi M, Kaibuchi K, Sobue K, Sawamoto. K.Speed control for neuronal migration in the postnatal brain by Gmip-mediated local inactivation of RhoA.Nat Commun. July 30;5:4532 (2014).
    4. Han YP, Ma CK, Wang SQ, Enomoto A, Zhao Y, Takahashi M, Ma J.Evaluation of osteopontin as a potential biomarker for central nervous system embryonal tumors.J Neuro-Oncol. 119:343-351 (2014).
    5. Kato T, Enomoto A, Watanabe T, Haga H, Ishida S, Kondo Y, Furukawa K, Urano T, Mii S, Weng L, Ishida-Takagishi M, Asai M, Asai N, Kaibuchi K, Murakumo Y, Takahashi M.TRIM27/MTRF-B-dependent integrin beta1 expression defines leading cells in cancer cell collecitives.Cell Rep. 7:1156-1167 (2014)
    6. Niimi K, Murakumo Y, Watanabe N, Kato T, Mii S, Enomoto A, Asai M, Asai N, Yamamoto E, Kajiyama H, Shibata K, Kikkawa F, Takahashi M.Suppression of REV7 enhances cisplatin sensitivity in ovarian clear cell carcinoma cellsCancer Sci. 105:545-552 (2014).
    7. Hagiwara D, Arima H, Morishita Y, Wenjun L, Azuma Y, Ito Y, Suga H, Goto M, Banno R, Sugimura Y, Shiota A, Asai N, Takahashi M, Oiso Y.Arginine vasopressin neuronal loss results from autophagy-associated cell death in a mouse model for familial neurohypophysial diabetes insipidus.Cell Death and Disease 5:e114 (2014).
    8. Miyachi H, Mii S, Enomoto A, Murakumo Y, Kato T, Asai N, Komori K, Takahashi M.Role of Girdin in intimal hyperplasia in vein grafts and efficacy of atelocollagen-mediated application of siRNA for vein failure.J Vasc Surg. 60:479-489.e5 (2014).
    9. Nishimae K, Tsunoda N, Yokoyama Y, Kokuryo T, Iwakoshi A, Takahashi M, Nagiono, M.The impact of Girdin expression on recurrence-free survival in patients with luminal-type breast cancer.Breast Cancer in press
    10. Qiao S, Fan K, Iwashita T, Ichihara M, Yoshino M, Takahashi M.The involvement of reactive oxygen species derived from NADPH oxidase-1 activation on the constitutive tyrosine auto-phosphorylation of RET proteins.Free Radic Res. 48:427-34 (2014).
    11. Sakakura H, Murakumo Y, Mii S, Hagiwara S, Kato T, Asai M, Hoshino A, Yamamoto N, Sobue S, Ichihara M, Ueda M, Takahashi M.Detection of a soluble form of CD109 in serum of CD109 transgenic and tumor xenografted mice.PLoS One. 9:e83385 (2014).
    12. Takahara Y, Maeda M, Hasegawa H, Ito S, Hyodo T, Asano E, Takahashi M, Hamaguchi M, Senga T.Silencing of TBC1D15 promotes RhoA activation and membrane blebbing.Mol Cell Biochem. 389:9-16 (2014).
    13. Hoshino A, Hanada S, Yamada H, Mii S, Takahashi M, Mitarai S, Yamamoto K, Manome Y.Mycobacterium tuberculosis escapes from the phagosomes of infected human osteoclasts reprograms osteoclast development via dysregulation of cytokines and chemokines.Pathog Dis. 70:28-39 (2014).
  • 2013年
    1. Ueno S, Nishiguchi KM, Tanioka H, Enomoto A, Yamanouchi T, Kondo M, Yasuma TR, Yasuda S, Kuno N, Takahashi M, Terasaki H.Degeneration of retinal on bipolar cells induced by serum including autoantibody against TRPM1 in mouse model of paraneoplastic retinopathy.PLoS One. 8:e81507 (2013).
    2. Ota H, Hikita T, Nishioka T, Matsumoto M, Ito J, Asai N, Enomoto A, Takahashi M, Kaibuchi K, Sobue K, Sawamoto K.Proteomic analysis of Girdin-interacting proteins in migrating new neurons in the postnatal mouse brain.Biochem Biophys Res Commun. 442:16-21 (2013).
    3. Asano E, Hasegawa H, Hyodo T, Ito S, Maeda M, Takahashi M, Hamaguchi M, Senga T.The Aurora-B-mediated phosphorylation of SHCBP1 regulates cytokinetic furrow ingression.J Cell Sci. 126:3263-3270 (2013).
    4. Hagiwara S, Yamamoto N, Furue H, Sakakura H, Shigetomi T, Murakumo Y, Hibi H, Takahashi M, Ueda M.Pathological analysis of Ki-67 and CD109 expression in tongue squamous cell carcinoma.J Oral Maxillofac Surg Med Pathol. 25:276-281 (2013).
    5. Watanabe, N., Mii, S., Asai, N., Asai, M., Niimi, K., Ushida, K., Kato, T., Enomoto, A., Ishii, H., Takahashi, M., and Murakumo, Y,The REV7 subunit of DNA polymerase ζ is essential for primordial germ cell maintenance in the mouse.J. Biol. Chem.288:10459-10471 (2013).
    6. Ito, T., Komeima, K., Yasuma, T., Enomoto, A., Asai, N., Iwase, S., Takahashi, M. and Terasaki, H.Girdin and its phosphorylation dynamically regulate neonatal vascular development and pathological neovascularization in the retina.Am. J. Pathol. 182: 586-596 (2013).
    7. An, J., Enomoto, A., Weng, L., Kato, T., Iwakoshi, A., Ushida, K., Maeda, K., Ishida-Takagishi, M., Ishii, G., Ming, S., Sun, T. and Takahashi, M.Significance of cancer-associated fibroblasts in the regulation of gene expression in the leading cells of invasive lung cancer.J. Cancer Res. Clin. Oncol. 139: 379-388 (2013).
  • 2012年
    1. Muteliefu G, Shimizu H, Enomoto A, Nishijima F, Takahashi M, Niwa T.Indoxyl sulfate promotes vascular smooth muscle cell senescence with upregulation of p53, p21, and prelamin A through oxidative stress.Am J Physiol Cell Physiol. 303:C126-134 (2012).
    2. Mao, J.-Z., Jiang, P., Cui, S.-P., Ren, Y.-L., Zhao, J., Yin, X.-H., Enomoto, A., Liu, H.-J., Hou, L., Takahashi, M. and Zhang, B.Girdin locates in centrosome and midbody and plays an important role in cell division.Cancer Sci. 103: 1780-1787 (2012).
    3. Horio-Sakurai, M., Kato, T., Mii, S., Enomoto, A., Asai, M., Asai, N., Murakumo, Y., Shibata, K., Kikkawa, F. and Takahashi, M.Expression of RET finger protein predicts chemoresistance in epithelial ovarian cancer.Cancer Med. 1: 218-229 (2012).
    4. Asai M., Asai, N., Murata, A., Yokota, H., Ohmori, K., Mii, S., Enomoto, A., Murakumo, Y. and Takahashi, M.Similar Phenotypes of Girdin germ-line and conditional knockout mice indicate a crucial role for Girdin in the nestin lineage.Biochem. Biophys. Res. Commun. 426: 533-538 (2012).
    5. Hyodo T, Ito S, Hasegawa H, Asano E, Maeda M, Urano T, Takahashi M, Hamaguchi M, Senga T.Misshapen-like kinase 1 (MINK1) Is a Novel Component of Striatin-interacting Phosphatase and Kinase (STRIPAK) and Is Required for the Completion of Cytokinesis.J. Biol. Chem. 287: 25019-25029 (2012).
    6. Mii, S., Murakumo, Y., Asai, N., Jijiwa, M., Hagiwara, S., Kato, T., Asai, M., Enomoto, A., Ushida, K., Sobue, S., Ichihara, M. and Takahashi, M.Epidermal hyperplasia and appendage abnormalities in mice lacking CD109.Am. J. Pathol. 181: 1180-1189 (2012).
    7. Muteliefu, G., Shimizu, H., Enomoto, A., Nishijima, F., Takahashi, M. and Niwa, T.Indoxyl sulfate promotes vascular smooth muscle cell senescence with upregulation of p53, p21 and prelamin A through oxidative stress.Am. J. Physiol. Cell Physiol. 303: C126-C134 (2012).
    8. Ishida-Takagishi, M., Enomoto, A., Asai, N., Ushida, K., Watanabe, T., Hashimoto, T., Kato, T., Weng, L., Matsumoto, S., Asai, M., Murakumo, y., Kaibuchi, K., Kikuchi, A. and Takahashi, M.The Dvl-associated protein Daple controls the non-canonical Wnt/Rac pathway and cell motility.Nature Commun. 3: 859 (2012).
    9. Ohara, K., Enomoto, A., Kato, T., Hashimoto, T., Isotani-Sakakibara, M., Asai, N., Ishida,-Takagishi, M., Weng, L., Nakayama, M., Watanabe, T., Kato, K., Kaibuchi, K., Murakumo, Y., Hirooka, Y., Goto, H. and Takahashi M.Involvement of Girdin in the dermination of cell polarity during cell migration.PLoS One, 7: e36681 (2012).
    10. Iwakoshi A., Murakumo Y., Kato T., Kitamura A., Mii S., Saito S., Yatabe Y., Takahashi M.RET finger protein expression is associated with prognosis in lung cancer with epidermal growth factor receptor mutations.Pathol. Int. 62: 324-330 (2012).
    11. Natsume, A., Kato, T., Kinjo, S., Enomoto, A., Toda, H., Shimato, S., Ohka, F., Motomura, K., Kondo, Y., Miyata, T., Takahashi, M. and Wakabayashi, T.Girdin maintains the stemness of glioblastoma stem cells.Oncogene 31: 2715-2724 (2012).
    12. Ohgami, N., Ida-Eto, M., Sakashita, N., Sone, M., Nakashima, T., Tabuchi, K., Hoshino, T., Shimada, A., Tsuzuki, T., Yamamoto, M., Sobue, G., Jijiwa, M., Asai, N., Hara, A., Takahashi, M. and Kato, M.Partial impairment of c-Ret at tyrosine 1062 accelerates age-related hearing loss in mice.Neurobiol. Aging 33: 626 e25-34 (2012).
    13. Kee, H. J., Kim, J-R, Joung, H., Choe, N., Lee, S. E., Eom, G. H., Kim, J. C., Geyer, S. H., Jijiwa, M., Kato, T., Kawai, K., Weninger, W. J., Seo, S. B., Nam, K-I., Jeong, M. H., Takahashi, M. and Kook, H.Ret finger protein inhibits muscle differentiation by modulating serum response factor and enhancer of polycomb 1.Cell Death Differ. 19: 121-131 (2012).
  • 2011年
    1. Nakamura, N., Naruse, K., Kobayashi, Y., Matsuki, T., Hamada, Y., Nakashima, E., Kamiya, H., Hata, M., Nishikawa, T., Enomoto, A., Takahashi, M., Murohara, T., Matsubara, T., Oiso, Y., Nakamura, J.High glucose impairs the proliferation and increases the apoptosis of endothelial progenitor cells by suppression of Akt.J. Diabetes Invest. 2: 262-270 (2011).
    2. Asano, E., Maeda, M., Hasegawa, H., Ito, S., Hyodo, T., Yuan, H., Takahashi, H., Hamaguchi, M. and Senga, T.Role of palladin phosphorylation by extracellular signal-regulated kinase in cell migration.PLOS One 6: e29338 (2011).
    3. Morishita, Y., Arima, H., Hiroi, M., Hayashi, M., Hagiwara, D., Asai, N., Ozaki, N., Sugiura, Y., Nagasaki, H., Shiota, A., Takahashi, M. and Oiso, Y.Poly(A) tail length of neurohypophysial hormones is shortened under endoplasmic reticulum.Endocrinology 152: 4846-4855 (2011).
    4. Kuroda, K., Yamada, S., Tanaka, M., Iizuka, M., Yano, H., Mori, D., Tsuboi, D., Nishioka, T., Namba, T., Iizuka, Y., Kubota, S., Nagai, T., Ibi, D., Wang, R., Enomoto, A., Isotani-Sakakibara, M., Asai, N., Kimura, K., Kiyonari, H., Abe, T., Mizoguchi, A., Sokabe, M., Takahashi, M., Yamada, K. and Kaibuchi, K.Behavioral alterations associated with targeted disruption of exons 2 and 3 of the DISC1 gene in the mouse.Hum. Mol. Genet. 20: 4666-4683 (2011).
    5. Huang, Z., Ichihara, S., Oikawa, S., Chang, J., Zhang, L., Takahashi, M., Subramanian, K., Mohideen, S. S., Wang, Y. and Ichihara, G.Proteomic analysis of hippocampal proteins of F344 rats exposed to 1-bromoprpane.Toxicol. Appl. Pharmacol. 257: 93-101 (2011).
    6. Motegi Y., Katayama K., Sakurai F., Kato T., Yamaguchi T., Matsui H., Takahashi M., Kawabata K., Mizuguchi H.An effective gene-knockdown using multiple shRNA-expressing adenovirus vectors.J. Control Release 153: 149-153 (2011).
    7. Wang, Y., Kaneko, N., Asai, N., Enomoto, A., Isotani-Sakakibara, M., Kato, T., Asai, M., Murakumo, Y., Ota, H., Hikita, T., Namba, T., Kuroda, K., Kaibuchi, K., Ming, G., Song, H., Sawamoto, K. and Takahashi, M.Girdin is an intrinsic regulator of neuroblast chain migration in the rostral migratory stream of the postnatal brain.J. Neurosci. 31: 8109-8122 (2011).
    8. Miyake, H., Maeda, K., Asai, N., Shibata, R., Ichimiya, H., Isotani-Sakakibara, M., Yamamura, Y., Kato, K., Enomoto, A., Takahashi, M. and Murohara, T.The actin-binding protein Girdin and its Akt-mediated phosphorylation regulate neointima formation after vascular injury.Circ. Res. 108: 1170-1179 (2011).
    9. Matsushita, E., Asai, N., Enomoto, A., Kawamoto, Y., Kato, T., Mii, S., Maeda, K., Shibata, R., Hattori, S., Hagikura, M., Takahashi, k., Sokabe, M., Murakumo, Y., Murohara, T. and Takahashi, M.Protective role of Gipie, a Girdin family protein, in endoplasmic reticulum stress responses in endothelial cell.Mol. Biol. Cell. 22: 736-747 (2011).
    10. Miyamoto, R., Jijiwa, M., Asai, M., Kawai, K., Ishida-Takagishi, M., Mii, S., Asai, N., Enomoto, A., Murakumo, Y., Yoshimura, A. and Takahashi, M.Loss of Sprouty2 partially rescues renal hypoplasia and stomach hypoganglionosis but not intestinal aganglionosis in Ret Y1062F mutant miceDev. Biol.349: 160-168 (2011).
    11. Saito, S., Murakumo, Y., Tsuzuki, T., Dambara, A., Kato, T., Enomoto, A., Asai, N., Maruyama, S., Matsuo, S. and Takahashi, M.Analysis of GDNF-inducible zinc finger protein 1 expression in human diseased kidney.Human Pathol. 42: 848-858 (2011).
  • 2010年
    1. Yamaguchi M., Suyari O., Nagai R., Takahashi M.dGirdin a new player of Akt /PKB signaling in Drosophila melanogaster.Front. Biosci. 15: 1164-1171 (2010).
    2. Hagikura, M., Murakumo, Y., Hasegawa, M., Jijiwa, M., Hagiwara, S., Mii, S., Hagikura, S., Matsukawa, Y., Yoshino, Y., Hattori, R., Wakai, K., Nakamura, S., Gotoh, M. and Takahashi, M.Correlation of pathological grade and tumor stage of urothelial carcinoma with CD109 expression.Pathol. Int. 60: 735-743 (2010).Ohgami, N., Ida-Eto, M., Shimotake, T., Sakashita, N., Sone, M., Nakashima, T., Tabuchi, K., Hoshino, T., Shimada, A., Tsuzuki, T., Yamamoto, M., Sobue, G., Jijiwa, M., Asai, N., Hara, A., Takahashi, M. and Kato, M.
    3. c-Ret-mediated hearing loss in mice with Hirschsprung disease.Proc. Natl. Acad. Sci. USA. 107: 13051-13056 (2010).
    4. Hagiwara, S., Murakumo, Y., Mii, S., Shigetomi, T., Yamamoto, N., Furue, H., Ueda, M. and Takahashi,M.Processing of CD109 by furin and its role in the regulation of TGF-beta signaling.Oncogene 29: 2181-2191.(2010)
    5. Kurotsuchi, A., Murakumo, Y., Jijiwa, M., Kurokawa, K., Itoh, Y., Kodama, Y., Kato, T., Enomoto, A.,Asai, N., Terasaki, H. and Takahashi, M.Analysis of DOK-6 function in downstream signaling of RET in human neuroblastoma cells.Cancer Sci. 101: 1147-1155 (2010).
    6. Weng, L., Enomoto, A., Ishida-Takagishi, M., Asai, N. and Takahashi, M.Girding for migratory cues: Role of the Akt substrate Girdin in cancer progression and angiogenesis.Cancer Sci. 101: 836-842 (2010).
    7. Kato, M., Takeda, K., Hossain, K., Thang, N.D., Kaneko, Y., Kumasaka, M., Yamanoshita, O., Uemura, N.,Takahashi, M., Ohgami, N., and Kawamoto, Y.A redox-linked novel pathway for arsenic-mediated RET tyrosine kinase activation.J. Cell. Biochem. 110: 399-407 (2010).
    8. Ohshima, Y., Yajima, I., Kumasaka, M.Y., Yanagishita, T., Watanabe, D., Takahashi, M., Inoue, Y., Ihn, H., Matsumoto, Y. and Kato, M.CD109 expression levels in malignant melanoma.J. Dermatol. Sci. 57: 140-142 (2010).
    9. Kumasaka, M.Y., Yajima, I., Hossain, K., Iida, M., Tsuzuki, T., Ohno, T., Takahashi, M., Yanagisawa,M. and Kato, M.A novel mouse model for de novo Melanoma.Cancer Res. 70: 24-29 (2010).
  • 2009年
    1. Muteliefu, G., Enomoto, A., Jiang, P., Takahashi, M., Niwa, T.Indoxyl sulphate induces oxidative stress and the expression of osteoblast-specific proteins in vascular smooth muscle cells.Nephrol. Dial. Transplant. 24: 2051-2058 (2009).
    2. Lu, B., Cebrian, C., Chi, X., Kuure, S., Kuo, R., Bates, C.M., Arber, S., Hassell, J., MacNeil, L., Hoshi, M., Jain, S., Asai, N., Takahashi, M., Schmidt-Ott, K., Barasch, J., D'Agati, V. and Costantini, F.Etv4 and Etv5 are required downstream of GDNF and Ret for kidney branching morphogenesis.Nature Genet. 41:1295-1302 (2009).
    3. Puseenam, A., Yoshioka, Y., Nagai, R, Hashimoto, R, Suyari, O, Itoh, M, Enomoto, A, Takahashi, M. and Yamaguchi, M.A novel Drosophila Girdin-like protein is involved in Akt pathway control of cell size.Exp. Cell Res. 315:3370-3380 (2009).
    4. Enomoto, A., Asai, N., Namba, T., Wang, Y., Kato, T., Tanaka, M., Tatsumi, H., Taya, S., Tsuboi, D., Kuroda, K., Kaneko, N., Sawamoto, K., Miyamoto, R., Jijiwa, M., Murakumo, Y., Sokabe, M., Seki, T., Kaibuchi, K. and Takahashi, M.Roles of Disrupted-in-Schizophrenia 1-interacting protein Girdin in postnatal development of the dentate gyrus.Neuron 63: 774-787 (2009).
    5. Tsukamoto, H., Kato, T., Enomoto, A., Nakamura, N., Shimono, Y., Jijiwa, M., Asai, N., Murakumo, Y., Shibata, K., Kikkawa, F. and Takahashi, M.Expression of Ret finger protein correlates with outcomes in endometrial cancer.Cancer Sci. 100: 1895-1901 (2009).
    6. Chi, X., Michos, O., Shakya, R., Riccio, P., Enomoto, H., Licht, J.D., Asai, N., Takahashi, M., Ohgami, N., Kato, M., Mendelsohn, C. and Costantini, FRet-dependent cell rearrangements in the Wolffian duct epithelium initiate ureteric bud morphogenesis.Dev. Cell 17: 199-209 (2009).
    7. Nakamura, N., Naruse, K., Matsuki, T., Hamada, Y., Nakashima, E., Kamiya, H., Matsubara, T., Enomoto, A., Takahashi, M, Oiso, Y. and Nakamura, J.Adiponectin promotes migration activities of endothelial progenitor cells via Cdc42/Rac1FEBS Lett. 583: 2457-2463 (2009).
    8. Kato, T., Shimono, Y., Hasegawa, M., Jijiwa, M., Enomoto, A., Asai, N., Murakumo, Y. and Takahashi, M.Characterization of the HDAC1 complex that regulates the sensitivity of cancer cells to oxidative stress.Cancer Res. 69: 3597-3604 (2009).
    9. Jiang, P., Enomoto, A. and Takahashi, M.Cell biology of the movement of breast cancer cells: intracellular signaling and the actin cytoskeleton.Cancer Lett. 284:122-130 (2009).
  • 2008年
    1. Hasegawa, T., Enomoto, A., Kato, T., Kawai, K., Miyamoto, R., Jijiwa, M., Ichiahara, M., Ishida, M., Asai, N., Murakumo, Y., Ohara, K., Niwa, Y., Goto, H., and Takahashi, M.Roles of induced expression of MAPK phosphatase-2 in tumor development in RET-MEN2A transgenic mice.Oncogene 27: 5684-5695 (2008).
    2. Hagiwara, S., Murakumo, Y., Sato, T., Mitsudo, K., Tohnai, I., Ueda, M. and Takahashi, M.Up-regulation of CD109 expression is associated with carcinogenesis of the squamous epithelium of the oral cavity.Cancer Sci. 99: 1916-1923 (2008).
    3. Hasegawa, M., Moritani, S., Murakumo, Y., Sato, T., Hagiwara, S., Suzuki, C., Mii, S., Jijiwa, M., Enomoto, a., Asai, N., Ichihara, S. and Takahashi, M.CD109 expression in basal-like breast carcinoma.Pathol. Int. 58: 288-294 (2008).
    4. Kitamura, T., Asai, N., Enomoto, A., Maeda, K., Kato, T., Ishida, M., Jiang, P., Watanabe, T., Usukura, J., Kondo, T., Costantini, F., Murohara, T. and Takahashi, M.Regulation of VEGF-mediated angiogenesis by the Akt/PKB substrate Girdin.Nature Cell Biol., 10:329-337(2008).
    5. Jiang, P., Enomoto, A., Jijiwa, M., Kato, T., Hasegawa, T., Ishida, M., Sato, T., Asai, N., Murakumo, Y. and Takahashi, M.An actin-binding protein Girdin regulates the motility of breast cancer cells.Cancer Res., 68:1310-1318(2008).
    6. Jijiwa, M., Kawai, K., Fukihara, J., Nakamura, A., Hasegawa, M., Suzuki, C., Sato, T., Enomoto, A., Asai, N., Murakumo, Y. and Takahashi, M.GDNF-mediated Signaling via RET Tyrosine 1062 is Essential for Maintenance of Spermatogonial Stem Cells.Genes Cells, 13:365-374(2008).
    7. Suzuki, C., Murakumo, Y., Kawase, Y., Sato, T., Morinaga, T., Fukuda, N., Enomoto, A., Ichihara, M. and Takahashi, M.A novel GDNF-inducible gene, BMZF3, encodes a transcriptional repressor associated with KAP-1.Biochem. Biophys. Res. Commun. 366: 226-232 (2008).
  • 2007年
    1. Ichihara, M., Murakumo, Y., Masuda, A., Matsuura, T., Asai, N., Jijiwa, M., Ishida, M., Shinmi, J., Yatsuya, H., Qiao, S., Takahashi, M. and Ohno, K.Thermodynamic instability of siRNA duplex is a prerequisite for dependable prediction of siRNA activities.Nucleic Acids Res. 35: e123 (2007).
    2. Sato, T. Murakumo, Y., Hagiwara, S., Jijiwa, M., Suzuki, C. and Takahashi, M.High level expression of CD109 in lung squamous cell carcinoma.Pathol. Int. 57: 719-724 (2007).
    3. Dambara, A., Morinaga, T., Fukuda, N., Yamakawa, Y., Kato, T., Enomoto, A., Asai, N., Murakumo, Y., Matsuo, S. and Takahashi, M.Nucleolin modulates the subcellular localization of GDNF-inducible zinc finger protein 1 and its roles in transcription and cell proliferation.Exp. Cell Res. 313: 3755-3766 (2007).
    4. Murakami, M., Ichihara, M., Sobue, S., Kikuchi, R., Ito H., Kimura, A., Iwasaki, T., Takagi, A., Kojima, T., Takahashi, M., Suzuki, M., Banno, Y., Nozawa, Y. and Murate, T.RET signaling-induced SPHK1 gene expression plays a role in both GDNF-induced differentiation and MEN2-type oncogenesis.J. Neurochem. 102: 1585-1594 (2007).
    5. Li, B., Zhou, J., Hu, J., Jin, H., Shimono, Y., Takahashi, M. and Xu, G.Polycomb protein Cbx4 promotes SUMO modification of de novo DNA methyltransferase Dnmt3a.Biochem. J. 405: 369-378 (2007).
    6. Ishida, M., Ichihara, M., Mii, S., Jijiwa, M., Asai, N., Enomoto, A., Kato, T., Majima, A., Jiang, P., Murakumo, Y. and Takahashi, M.Sprouty2 regulates growth and differentiation of human neuroblastoma cells through RET tyrosine kinase.Cancer Sci. 98: 815-821 (2007).
    7. Hasegawa, M., Hagiwara, S., Sato, T., Jijiwa, M., Murakumo, Y., Maeda, M., Moritani, S., Ichihara, S. and Takahashi, M.CD109, a new marker for myoepithelial cells of mammary, salivary, and lacrimal glands and prostate basal cellsPathol. Int. 57: 245-250 (2007).
    8. Kee, H. J., Kim, J-R., Nam, K-I., Park, H. Y., Shin, S., Kim, J. C., Shimono, Y., Takahashi, M., Jeong, M. H., Kim, N., Kim, K. K. and Kook, H.Enhancer of Polycomb1, a novel homeodomain only protein binding partner, induces skeletal muscle differentiation.J. Biol. Chem. 282: 7700-7709 (2007).
    9. Kato, M., Ohgami, N., Kawamoto, Y., Tsuzuki, T., Hossain, K., Yanagishita, T., Ohshima, Y., Tsuboi, H., Yamanoshita, O., Matsumoto, Y., Takahashi, M. and Nakashima, I.Protective effect of hyperpigmented skin on UV-mediated cutaneous cancer development.J. Invest. Dermatol. 127: 1244-1249 (2007).
  • 2006年
    1. Asai, N., Fukuda, T., Wu, Z., Enomoto, A., Pachnis, V., Takahashi, M. and Costantini, F.Targeted mutation of serine 697 in the Ret tyrosine kinase causes migration defect of enteric neural crest cells.Development 133: 4507-4516 (2006).
    2. Murakumo, Y., Jijiwa, M., Asai, N., Ichihara, M., and Takahashi, M.RET and neuroendocrine tumors.Pituitary 9: 179-192 (2006).
    3. Enomoto, A., Jiang, P., and Takahashi, M.Girdin, a novel actin-binding protein, and its family of proteins posses versatile function in the Akt and Wnt signaling pathways.Ann. NY Acad. Sci., 1086: 169-184 (2006).
    4. Kato, M., Takeda, K., Kawamoto, Y., Tsuzuki, T., Kato, Y., Ohno, T., Hossain, K., Iftakhar-E-Khuda, I., Ohgami, N., Isobe, K., Takahashi, M. and Nakashima, I.Novel hairless RET-transgenic mouse line with melanocytic nevi and anagen hair follicles.J. Invest. Dermatol. 126: 2547-2550 (2006).
    5. Uchida, M., Enomoto, A., Fukuda, T., Kurokawa, K., Maeda, K., Kodama, Y., Asai, N., Hasegawa, T., Shimono, Y., Jijiwa, M., Ichihara, M., Murakumo, Y. and Takahashi, M.Dok-4 regulates GDNF-dependent neurite outgrowth through downstream activation of Rap1 and mitogen-activated protein kinase.J. Cell Sci. 119: 3067-3077 (2006).
    6. Takeda, K., Kawamoto, Y., Okuno, Y, Kato, M., Takahashi, M., Suzuki, H., Isobe, K. and Nakashima, I.A PKC-mediated backup mechanism of the MXXCW motif-linked switch for initiating tyrosine kinase activities.FEBS Lett. 839-843 (2006).
    7. Asai, N., Jijiwa, M., Enomoto, A., Kawai, K., Maeda, K., Ichihara, M. and Takahashi M.RET receptor signaling; Dysfunction in thyroid cancer and Hirschsprung’s disease.Pathol. Int. 56: 164-172 (2006).
    8. Murakumo, Y., Mizutani, S., Yamaguchi, M., Ichihara, M. and Takahashi, M.Analyses of ultraviolet-induced focus formation of hREV1 protein. C Genes Cells 11: 193-205 (2006).
  • 2005年
    1. Zhang JM, Hashimoto M, Kawai K, Murakumo Y, Sato T, Ichihara M, Nakamura S, Takahashi M.CD109 expression in squamous cell carcinoma of the uterine cervixPathol Int. 55: 165-169 (2005).
    2. Shimono, K., Shimono, Y., Shimokata, K., Ishiguro, N., and Takahashi, M.Microspherule protein 1, Mi-2β, and RET finger protein associate in the nucleolus and up-regulate ribosomal gene transcription.J. Biol. Chem. 280: 39436-39447 (2005).
    3. Enomoto, A., Murakami, H., Asai, N., Morone, N., Watanabe, T., Kawai, K., Murakumo, Y., Usukura, J., Kaibuchi, K., and Takahashi, M.Akt/PKB regulates actin organization and cell motility via Girdin/APE.Developmental Cell 9: 389-402 (2005).
    4. Morinaga, T., Enomoto, A., Shimono, Y., Hirose, F., Fukuda, N., Dambara, A., Jijiwa, M., Kawai, K., Hashimoto, K., Ichihara, M., Asai, N., Murakumo, Y., Matsuo, S., and Takahashi, M.GDNF-inducible zinc finger protein 1 is a sequence-specific transcriptional repressor that binds to the HOXA10 gene regulatory region.Nucleic Acids Res. 33: 4191-4201, 2005.
    5. Matsuura, T., Shimono, Y., Kawai, K., Murakami, H., Urano, T., Niwa, Y., Goto, H., and Takahashi, M.PIAS proteins are involved in the SUMO-1 modification, intracellular translocation and transcriptional repressive activity of RET finger protein.Exp. Cell Res. 308: 65-77, 2005.
    6. Fukuda, T., Asai, N., Enomoto, A., and Takahashi, M.Activation of c-Jun amino-terminal kinase by GDNF induces G2/M cell cycle delay linked with actin reorganization.Genes Cells, 10: 655-663, 2005.
    7. Kodama, Y., Asai, N., Kawai, K., Jijiwa, M., Murakumo, Y., Ichihara, M., and Takahashi, T.The RET proto-oncogene: a molecular therapeutic target in thyroid cancer.Cancer Sci. 96:143-148, 2005.
  • 2004年
    1. Jijiwa, M., Fukuda, T., Kawai, K., Nakamura, A., Kurokawa, K., Murakumo, Y., Ichihara, M. and Takahashi, M.A targeting mutation of tyrosine 1062 in Ret causes a marked decrease of enteric neurons and renal hypoplasia.Mol. Cell. Biol. 24: 8026-8036 (2004).
    2. Maeda, K., Murakami, H., Yoshida, R., Ichihara, M., Abe, A., Hirai, M., Murohara, T. and Takahashi, M.Biochemical and biological responses induced by coupling of Gab1 to phosphatidylinositol 3-kinase in RET-expressing cells.Biochem. Biophys. Res. Commun. 323: 345-354 (2004).
    3. Kodama, Y., Murakumo, Y., Ichihara, M., Kawai, K., Shimono, Y. and Takahashi, M.Induction of CRMP-2 by GDNF and analysis of the CRMP-2 promoter region.Biochem. Biophys. Res. Commun. 320:108-115 (2004).
    4. Hashimoto, T., Ichihara, M., Watanabe, T., Kawai, K., Koshikawa, K., Yuasa, N., Takahashi, T., Yatabe, Y., Murakumo, Y., Zhang, J.-m., Nimura, Y. and Takahashi, M.Expression of CD109 in human cancer.Oncogene 23: 3716-3720 (2004).
    5. Kawamoto, Y., Takeda, K., Okuno, Y., Yamakawa, Y., Ito, Y., Taguchi, R., Kato, M., Suzuki, H., Takahashi, M. and Nakashima, I.Identification of RET autophosphorylation sites by mass spectrometry.J. Biol. Chem. 279: 14213-14224 (2004).
    6. Kato, M., Takdea, K., Kawamoto, Y., Tsuzuki, T., Hossain, K., Tamakoshi, A., Kunisada, T., Kobayashi, Y., Ogino, K., Suzuki, H., Takahashi, M. and Nakahsima, I.c-Kit-targeting immunotherapy for hereditary melanoma in a mouse model.Cancer Res. 64: 801-806 (2004).
    7. Ichihara, M., Murakumo, Y., and Takahashi, M.RET and neuroendocrine tumors.Cancer Lett. 204:197-211 (2004).
  • 2003年
    1. Shimono, Y., Murakami, H., Kawai, K., Wade, P.A., Shimokata, K. and Takahashi, M.Mi-2 associates with BRG1 and RET finger protein at the distinct regions with transcriptional activating and repressing abilities.J. Biol. Chem. 278: 51638-51645 (2003).
    2. Kawai, K., Jijiwa, M., Shimono, Y., Kurokawa, K., Murakumo, Y., Ichihara, M. and Takahashi, M.Establishment and characterization of mouse mammary carcinoma cell lines expressing RET with a multiple endocrine neoplasia 2A mutation.Cancer Science 94: 992-997 (2003).
    3. Fukuda, N., Ichihara, M., Morinaga, T., Kawai, K., Hayashi, H., Murakumo, Y., Matsuo, S. and Takahashi, M.Identification of a novel GDNF-inducible gene required for renal branching morphogenesis.J. Biol. Chem. 278: 50386-50392 (2003).
    4. Shimoyama, Y., Morikawa, Y., Ichihara, M., Kodama, Y., Fukuda, N., Hayashi, H., Morinaga, T., Iwashita, T., Murakumoa, Y. and Takahashi, M.Identification of human SEP1 as a glial cell line-derived neurotrophic factor-inducible protein and its expression in the nervous system.Neuroscience 12: 899-906 (2003).
    5. Kurokawa, K., Kawai, K., Hashimoto, M., Ito, Y. and Takahashi M.Cell signaling and gene expression mediated by RET tyrosine kinase.J. Int. Med. 253: 627-633(2003).
    6. Ohshima, N., Takahashi, M. and Hirose, F.Identification of a human homologue of the DREF transcription factor with a potential role in regulation of the histone H1 gene.J. Biol. Chem. 278: 22928-22938(2003).
    7. Kawajiri, A., Yasui, Y., Goto, H., Tatsuka, M., Takahashi, M., Nagata, K. and Inagaki, M.Functional significance of Aurora-B in the separation of type III intermediated filaments during cytokinsis.Mol. Biol. Cell. 14: 1489-1500(2003).
    8. Nishikawa, M., Murakumo, Y., Imai, T., Kawai, K., Nagaya, M., Funahashi, H., Nakao, M. and Takahashi, M.Cys611Ser mutation in RET proto-oncogene is a kindred with medullary thyroid carcinoma and Hirschsprung’s disease.Eur. J. Human Genet. 11: 364-368(2003).
    9. Nakayama, A., Murakami, H., Maeyama, N., Yamashiro, N., Sakakibara, A., Mori, N. and Takahashi, M.Role for RFX transcription factors in non-neuronal cell-specific inactivation of the microtubule-associated protein MAP1A promoter.J. Biol. Chem. 278: 233-240 (2003).
  • 2002年
    1. Murakami, H., Yamamura, Y., Shimono, Y., Kawai, K., Kurokawa, K. and Takahashi, M.Role of Dok1 in cell signaling mediated by RET tyrosine kinase.J. Biol. Chem. 277: 32781-32790 (2002).
    2. Watanabe, T., Ichihara, M., Hashimoto, M., Shimono, K., Shimoyama, Y., Nagasaka, T., Murakumo, Y., Murakami, H., Sugiura, H., Iwata, H., Ishiguro, N. and Takahashi, M.Characterization of gene expression induced by RET with MEN2A or MEN2B mutation.Am. J. Pathol. 161: 249-256 (2002).
    3. Fukuda, T., Kiuchi, K. and Takahashi, M.Essential role for protein kinase A in Rac activity mediated by RET tyrosine kinase.J. Biol. Chem. 277: 19114-19121 (2002).
    4. Kato, M., Takeda, K., Kawamoto, Y., Iwashita, T., Akhand, A.A., Senga, T., Yamamoto, M., Sobue, G., Hamaguchi, M., Takahashi, M. and Nakashima, I.Repair by Src kinase of functional-impaired RET with multiple endocrine neoplasia type 2A mutation with substitutions of tyrosines in the COOH-terminal kinase domain for phenylalanine.Cancer Res. 62: 2414-2422 (2002).
    5. Iwahashi, N., Nagasaka, T., Tezel, G., Iwashita, T., Asai, N., Murakumo, Y., Kiuchi, K., Sakata, K., Nimura, Y. and Takahashi, M.Expression of glial cell line-derived neurotrophic factor correlates with perineural invasion of bile duct carcinoma.Cancer 94: 167-174 (2002).
  • 2001年
    1. Murakumo, Y., Ogura, Y., Ishii, H., Numata, S., Ichiahra, M., Croce, C. M., Fichel, R. and Takahashi, M.Interaction in the error-prone psot-replication repair proteins, hREV1, hREV3, and hREV7.J. Biol. Chem. 276: 35644-35661 (2001).
    2. Kato, M., Takeda, K., Kawamoto, Y., Tsuzuki, T., Dai, Y., Nakayama, S., Toriyama, K., Tamada, Y., Takahashi, M. and Nakashima, I.RET tyrosine kinase enhances hair growth in association with promotion of melanogensis.Oncogene 20: 7536-7541 (2001).
    3. Takahashi, M.The GDNF/RET signaling pathway and human diseases.Cysokine & Growth Factor Reviews 12: 361-373 (2001).
    4. Iwashita, T., Kurokawa, K., Qiao, S., Murakami, H., Asai, N., Kawai, K., Hashimoto, M., Watanabe, T., Ichihara., M. and Takahashi, M.Functional analysis of RET with Hirschsprung's mutations affecting its kinase domain.Gastroenterology 121: 24-33 (2001).
    5. Shigemitsu, K., Sekido, Y., Usami, N., Mori, S., Sato, M., Horio, Y., Hasegawa, Y., Bader, S.A., Gazdar, A.F., Minna, J.D., Hida, T., Yoshioka, H., Imaizumi, M., Ueda, Y., Takahashi, M. and Shimokata, K.Genetic alteration of the b-catenin gene (CTNNB1) in human lung cancer and malignant mesothelioma and identification of a new 3p21.3 homozygous deletion.Oncogene 20: 4249-4257 (2001).
    6. Kurokawa, K., Iwashita, T., Murakami, H., Hayashi, H., Kawai, K. and Takahashi, M.Identification of SNT/FRS2 docking site on RET receptor tyrosine kinase and its role for signal transduction.Oncogene 20: 1929-1938 (2001).
    7. Qiao, S., Iwashita, T., Furukawa, T., Yamamoto, M., Sobue, G. and Takahashi, M.Differential effects of leukocyte common antigen-related protein on biochmical and biological activities of RET-MEN2A and RET-MEN2B mutant proteins.J. Biol Chem. 276: 9460-9467 (2001).
    8. Hayashi, Y., Iwashita, T., Murakami, H., Kato, Y., Kawai, K., Tohnai, I., Ueda, M. and Takahashi, M.Activation of BMK1 via tyrosine 1062 in RET by GDNF and MEN2A mutation.Biochem. Biophys. Res. Commun. 281: 682-689 (2001).
  • 2000年
    1. Shimono, Y., Murakami, H., Hasegawa, Y. and Takahashi, M.RFP is a transcriptional repressor and interacts with enhancer of polycomb that has dual transcriptional functions.J. Biol Chem. 275: 39411-39419. (2000).
    2. Kawai, K., Iwashita, T., Murakami, H., Hiraiwa, N., Yoshiki, A., Kusakabe, M., Ono, K., Iida, K., Nakayama, A. and Takahashi, M.Tissue-specific carcinogenesis in transgenic mice expressing the RET proto-oncogene with a multiple endocrine neoplasia type 2A mutation.Cancer Res. 60: 5254-5260 (2000).
    3. Hayashi, H., Ichihara, M., Iwashita, T., Murakami H., Shimono, Y., Kawai, K., Kurokawa K., Murakumo, Y., Imai, T., Funahashi, H., Nakao, A. and Takahashi, M.Characterization of intracellular signals via tyrosine 1062 in RET activated by glial cell-lined derived neurotrophic factor.Oncogene 19: 4469-4475 (2000).
    4. Iwashita, T., Murakami, H., Kurokawa, K., Kawai, K., Miyauchi, A., Futami, H., Qiao, S., Ichihara, M. and Takahashi, M.A two-hit model for development of multiple endocrine neoplasia type 2B by RET mutations.Biochem. Biophys. Res. Commun. 268: 804-808 (2000).
    5. Kato, M., Iwashita, T., Takeda, K., Akhand, A. A., Liu, W., Yoshihara, M., Asai N., Suzuki, H., Takahashi, M. and Nakashima, I.Ultraviolet light induces redox reaction-mediated dimerization and superactivation of oncogenic ret tyrosine kinases.Mol. Biol. Cell 11: 93-101 (2000).
  • 1999年
    1. Tezel, G. Nagasaka, T., Iwahashi, N., Asai N., Iwashita, T., Sakata, K. and Takahashi, M.Different nuclear/cytoplasmic distributions of RET finger protein (RFP) in different cell types.Pathol. Int. 49: 881-886 (1999)
    2. Ishiguro, Y., Iwashita, T., Murakami, H., Asai, N., Iida, K., Goto, H., Hayakawa, T. and Takahashi, M.The role of amino acids surrounding tyrosine 1062 in Ret in specific binding of the Shc phosphtyrosine binding domain.Endocrinology 140: 3992-3998 (1999).
    3. Murakami, H., Iwashita, T., Asai, N., Shimono, Y., Iwata, Y., Kawai, K. and Takahashi, M.Enhanced phosphatidylinositol 3-kinase activity and high phosphrylation state of its downstream signaling molecules mediated by Ret with the MEN 2B mutation.Biochem. Biophys. Res. Commun. 262: 68-75 (1999).
    4. Iwata, Y., Nakayama, A., Murakami, H., Iwashita, T., Asai, N. and Takahashi, M.Characterization of the promoter region of the human RFP gene.Biochem. Biophys. Res. Commun. 261: 381-384 (1999).
    5. Iwashita, T., Kato, M., Murakami, H., Asai, N., Ishiguro, Y., Ito, S., Iwata, Y., Kawai, K., Asai, M., Kurokawa, K., Kajita, H. and Takahashi, M.Biological and biochemical properties of Ret with kinase domain mutations identified in multiple endocrine neoplasia type 2B and familial medullary thyroid carcinoma.Oncogene 18: 3919-3922 (1999).
    6. Nakayama, S., Iida, K., Tsuzuki, T., Iwashita, T., Murakami, H., Asai, N., Iwata, Y., Ichihara, M., Ito, S., Kawai, K., Asai, M., Kurokawa, K. and Takahashi M.Implication of expression of GDNF/Ret signalling components in differentiation of bone marrow hematopoietic cells.Brit. J. Hematol. 105: 50-57 (1999).
    7. Takahashi, M., Iwashita, T., Santoro, M., Lyonnet, S., Lenor, G. M. and Billaud, M.Co-segregation of MEN2 and Hirschsprung's disease: the same mutation of RET with both gain and loss-of-function?Hum. Mutat. 13: 331-336 (1999).
    8. Murakami, H., Iwashita, T., Asai, N., Iwata, Y., Narumiya, S. and Takahashi, M.Rho-dependent and -independent tyrosine phosphorylation of focal adhesion kinase, paxillin and p130Cas mediated by Ret kinase.Oncogene 18: 1975-1982 (1999).
    9. Ohyabu, A., Higo, K., Ye, C., Amo, H., Saito, M., Yagyu, S., Morita, H., Maeda, K., Serikawa, T., Takahashi, M. and Matsuyama, M.Genetic mapping of the thymoma susceptible locus, Tsr1, in BUF/Mna rats.J. Natl. Cancer Inst. 91: 279-282 (1999).
  • 1998年
    1. Kato, M., Liu, W., Asai, N., Hayakawa, A., Kozaki, K., Takahashi, M. and Nakashima, I.The herbal medicine Sho-saiko-to inhibits grrowth and metastasis of malignant melanoma primarily developed in ret-transgenic mice.J. Invest. Dermatol. 111: 640-644 (1998).
    2. Kato, M., Takahashi, M., Asai, N., Liu, W., Shimizu, S., Iwamoto, T., Suzuki, H. and Nakashima, I.Transgenic mouse model for skin malignant melanoma.Oncogene 17: 1885-1888 (1998).
    3. Takahashi, M., Asai, N., Iwashita, T., Murakami, H. and Ito, S.Mechanisms of development of multiple endocrine neoplasia type 2 and Hirschsprung’s disease.Recent Results in Cancer Research 154: 229-236 (1998).
    4. Takahashi, M., Asai, N., Iwashita, T., Murakami, H. and Ito, S.Molecular mechanisms of development of multiple endocirine neoplasia 2 by RET mutations.J. Int. Med. 243: 509-513 (1998).
    5. Nozaki, C., Asai, N., Murakami, H., Iwashita, T., Iwata, Y., Horibe, K., Klein, R.D., Rosenthal, A. and Takahashi, M.Calcium-dependent Ret activation by GDNF and neurturin.Oncogene 16, 293-299 (1998).
  • 1997年
    1. Ito, S., Iwashita, T., Asai, N., Murakami, H., Iwata, Y., Sobue, G. and Takahashi, M.Biological properties of Ret with cysteine mutations correlate with multiple endocrine neoplasia type 2A, familial medullary thyroid carcinoma, and Hirschsprung's disease phenotype.Cancer Res. 57, 2870-2872 (1997).
    2. Klein, R.D., Sherman, D., Ho, W.-H., Stone, D., Bennett, G.L., Moffat, B., Vandlen, R., Simmons, L., Gu, Q., Hongo, A.-J., Devaux, B., Poulsen, K., Armanini, M., Nozaki, C., Asai, N., Goddard, A., Phillips, H., Henderson, C.E., Takahashi, M. and Rosenthal, A.A GPI-linked protein that interacts with Ret to form a candidate neurturin receptor.Nature 387, 717-721 (1997).
    3. Ohiwa, M., Murakami, H., Iwashita, T., Asai, N., Iwata, Y., Imai, T., Funahashi, H., Takagi, H. and Takahashi, M.Characterization of Ret-Shc-Grb2 complex induced by GDNF, MEN 2A and MEN 2B mutations.Biochem. Biophys. Res. Commun. 237, 747-751 (1997).
  • 1996年
    1. Iwashita, T., Murakami, H., Asai, N. and Takahashi, M.Mechanism of Ret dysfunction by Hirschsprung mutations affecting its extracellular domain.Hum. Mol. Genet. 5, 1577-1580 (1996).
    2. Asai, N., Murakami, H., Iwashita, T. and Takahashi, M.A mutation at tyrosine 1062 in MEN2A-Ret and MEN2B-Ret impairs their transforming activity and association with Shc adaptor proteins.J. Biol. Chem. 271, 17644-17649 (1996).
    3. Treanor, J.J.S., Goodman, L., de Sauvage, F., Stone, D.M., Poulsen, K.T., Beck, C.D., Gray, C., Armanini, M.P., Pollock, R.A., Hefti, F., Phillips, H.S., Goddard, A., Moore, M.W., Buj-Bello, A., Davies, A.M. Asai, N., Takahashi, M., Vandlen, R., Henderson, C.E. and Rosenthal, A.Characterization of a multicomponent receptor for GDNF.Nature 382, 80-83 (1996).
    4. Iwashita, T., Asai, N., Murakami, H., Matsuyama, M. and Takahashi, M.Identification of tyrosine residues that are essential for transforming activity of the ret proto-oncogene with MEN2A or MEN2B mutation.Oncogene 12, 481-487 (1996).
  • 1995年
    1. Asai, N., Iwashita, T., Matsuyama, M. and Takahashi, M.Mechanism of activation of the ret proto-oncogene by multiple endocrine neoplasia 2A mutations.Mol. Cell. Biol. 15, 1613-1619 (1995).
    2. Takahashi, M.Oncogenic activation of the ret protooncogene in thyroid cancer.Crit. Rev. Oncog. 6, 35-46 (1995).
    3. Tsuzuki, T., Takahashi, M., Asai, N., Iwashita, T., Matsuyama, M. and Asai, J.Spatial and temporal expression of the ret proto-oncogene product in embryonic, infant and adult rat tissues.Oncogene 10, 191-198 (1995).
  • 1993年
    1. Iwamoto, T., Taniguchi, M., Asai, N., Ohkusu, K., Nakashima, I. and Takahashi, M.cDNA cloning of mouse ret proto-oncogene and its sequence similarity to the cadherin superfamily.Oncogene 8, 1087-1091 (1993).
    2. Takahashi, M., Asai, N., Iwashita, T., Isomura, T., Miyazaki, K. and Matsuyama, M.Characterization of the ret proto-oncogene products expressed in mouse L cells.Oncogene 8, 2925-2929 (1993).
  • 1991年
    1. Iwamoto, T., Takahashi, M., Ito, M., Hamatani, M., Ohbayashi, M., Wajjwalku, W., Isobe, K. and Nakashima I.Aberrant melanogenesis and melanocytic tumor development in transgenic mice that carry a metallothionein/ret fusion gene.EMBO J. 10, 3167-3175 (1991).
    2. Takahashi, M., Buma, Y. and Taniguchi, M.Identification of the ret proto-oncogene products in neuroblastoma and leukemia cells.Oncogene 6, 297-301 (1991).
  • 1988年
    1. Takahashi, M., Buma, Y., Iwamoto, T., Inaguma, Y., Ikeda, H. and Hiai, H.Cloning and expression of the ret proto-oncogene encoding a tyrosine kinase with two potential transmembrane domain.Oncogene 3, 571-578 (1988).
    2. Takahashi, M., Inaguma, Y., Hiai, H. and Hirose, F.Developmentally regulated expression of a human finger-containing gene encoded by the 5’ half of the ret proto-oncogene.Mol. Cell. Biol. 7, 1853-1856 (1988).
  • 1987年
    1. Takahashi, M. and Cooper, G. M.ret transforming gene encodes a fusion protein homologous to tyrosine kinases.Mol. Cell. Biol. 7, 1378-1385 (1987).
  • 1985年
    1. Takahashi, M., Ritz, J. and Cooper, G.M.Activation of a novel human transforming gene, ret, by DNA rearrangement.Cell 42, 581-588 (1985).

研究キーワード

腫瘍、RET CD109 Girdin