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1996 Fiscal Year Final Research Report Summary

Wilms tumor suppressor gene WT1 blocks cell cycle progression

Research Project

Project/Area Number 07457580
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionOsaka University

Principal Investigator

AKIYAMA Tetsu  Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University Professor, 微生物病研究所, 教授 (70150745)

Project Period (FY) 1995 – 1996
Keywordstumor suppressor gene / Wilms tumor / cell cycle / WT1 / Glarrest / apoptosis / leukemia / M1
Research Abstract

We previously demonstrated that overexpression of the Wilms tumor suppressor gene WT1 blocks cell cycle progression from the G1 to S phase. However, we also found that WT1 is highly expressed in human hematopoietic malignancy and there exists a correlation between the levels of WT1 expression and a poor prognosis. Furthermore, suppression of WT1 expression by WT1 anti-sense oligonucleotide inhibits proliferation of leukemia cells. These results suggest that WT1 is important for the proliferation of leukemia cells. To further elucidate the biological significance of WT1 in leukemic cell growth, we overexpressed exogenous WT1 in murine M1 myeloblastic leukemia cells using the IPTG-controlled expression system. We found that induction of WT1 in M1 cells induces G1 arrest and apoptotic cell death. Thus the role of WT1 seems to be different depending on the type of leukemia cell in which it is expressed. We are now trying to isolate cDNAs the expression of which is changed by the action of WT1.

  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] T. Kudoh et al.: "G1 phase arrest induced by Wilms tumor protein WT1 is abrogated by cyclin/CDK" Proc. Natl. Acad. Sci. USA.92. 4517-4521 (1995)

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      「研究成果報告書概要(和文)」より
  • [Publications] T. Kudoh et al.: "Constitutive Expression of the Wilms tumor suppressor gene WT1 in F9 embryonal carcinoma cells induces apoptotice cell death in response to retinionic acid." Oncogene.13. 1431-1439 (1996)

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      「研究成果報告書概要(和文)」より
  • [Publications] 松村正: "「がん 最新知見から病態をとらえる」" メジカルビュー社, 160 (1997)

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      「研究成果報告書概要(和文)」より
  • [Publications] T.Kudoh, T.Ishidate, M.Moriyama, K.Toyoshima and T.Akiyama: "G1 phase arrest induced by Wilms tumor protein WT1 is abrogated by cyclin/CDK" Proc.Natl.Acad.Sci.USA.92. 4517-4521 (1995)

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      「研究成果報告書概要(欧文)」より
  • [Publications] I.Miyashiro, T.Senda, A.Matsumine, G.-H.Baeg, T.Kuroda, T.Shimano, S.Miura, T.Noda, S.Kobayashi, M.Monden, K.Toyoshima & T.Akiyama: "Subcellular localization of the APC protein : Immunoelectron microscopic study of the association of the APC protein with catenin" Oncogene. 11. 89-96 (1995)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Dobashi, T.Kudoh, A.Matsumine, K.Toyoshima & T.Akiyama: "Constitutive overexpression of Cdk2 inhibits neuronal differentiation of rat pheochromocytoma PC12 cells" J.Biol.Chem.270. 23031-23037 (1995)

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  • [Publications] G.-H.Baeg, A.Matsumine, T.Kuroda, R.N.Bhatacharjee, I.Miyashiro, K.Toyoshima & T.Akiyama: "The tumor suppressor gene product APC blocks cell cycle progression from the G0/G1 to S phase" EMBO J.14. 5618-5625 (1995)

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  • [Publications] A.Matsumine, T.Senda, G.-H.Baeg, B.C.Roy, Y.Nakamura, M.Noda, K.Toyoshima and T.Akiyama: "The MCC gene product regulates cell cycle transition from G0/G1 to S phase" J.Biol.Chem.271. 10341-10346 (1996)

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  • [Publications] T.Senda, I.Miyashiro, A.Matsumine, G.-H.Baeg, T.Monden, S.Kobayashi, M.Monden, K.Toyoshima & T.Akiyama: "The tumor suppressor protein APC colocalizes with beta-catenin in the colon epithelial cells" Biochem.Biophys.Res.Commun.223. 329-334 (1996)

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  • [Publications] I.Miyashiro, T.Kaname, T.Nakayama, S.Nakamori, T.Yagyu, T.Monden, N,Kikkawa, I.Nishisho, T.Muramatsu, M.Monden & T.Akiyama: "Expression of truncated midkine in human colorectal cancers" Cancer Letters. (in press).

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  • [Publications] Y.Dobashi, R.N.Bhattacharjee, K.Toyoshima & T.Akiyama: "Upregulation of the APC gene product during neuronal differentiation of rat pheocheromocytoma PC12 cells" Res.Commun.224. 479-483 (1996)

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      「研究成果報告書概要(欧文)」より
  • [Publications] T.Kudoh, T.Ishidate, K.Toyoshima & T.Akiyama: "Constitutive expression of the Wilms tumor suppressor gene WT1 in F9 embryonal carcinoma cells induces apoptotic cell death in response to retinoic acid." Oncogene.13. 1431-1439 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Adachi, S.Matsubara, C.Pedraza, M.Ozawa, J.Tsutsui, H.Takamatsu, H.Noguchi, T.Akiyama & T.Muramatsu: "Midkine as a novel target gene for the Wilms'tumor suppressor gene (WT1)" Oncogene.13. 2197-2203 (1996)

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  • [Publications] O.Higuchi, G.-H.Baeg, T.Akiyama & K.Mizuno: "Suppression of fibroblast cell growth by overexpression of LIM-containing protein kinase 1" FEBS LETTERS. 396. 81-86 (1996)

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  • [Publications] T.Yamagami, H.sugiyama, , K.Inoue, H.Ogawa, T.Tatekawa, M.Hirata, T.Kudoh, T.Akiyama, A.Murakami, T.Maekawa & T.Kishimoto: "Growth inhibition of human leukemic cells by WT1 (Wilms tumor gene) antisense oligodeoxynucleotides : implications for the involvement of WT1 in leukemogenesis" Blood.87. 2878-2884 (1996)

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  • [Publications] R.N.Bhattacharjee, F.Hamada, K.Toyoshima & T.Akiyama: "The tumor suppressor gene product APC is hyperphosphorylated during the M phase" Biochem.Biophys.Res.Commun.220. 192-195 (1996)

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  • [Publications] Y.Dobashi, T.Kudoh, K.Toyoshima & T.Akiyama: "Persistent activation of CDK4 during neuronal differentiation of rat pheochromocytoma PC12 cells" Biochem.Biophys.Res.Commun.221. 351-355 (1996)

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  • [Publications] A.Matsumine, A.Ogai, T.Senda, N.Okumura, K.Satoh, G.-H.Baeg, T.Kawahara, S.Kobayashi, M.Okada, K.Toyoshima & T.Akiyama: "Binding of APC to the human homolog of the Drosophila Discs large tumor suppressor protein" Scinece. 272. 1020-1023 (1996)

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  • [Publications] Y.Furukawa, T.Kawakami, K.Sudo, J.Inazawa, A.Matsumine, T.Akiyama and Y.Nakamura: "Isolation and mapping of a human gene (RPD3L1) that is homologous to RPD3, a transcription factor in Saccharomyces cerevisiae" Cytogenet.Cell Genet.73. 130-133 (1996)

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Published: 1999-03-09  

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