1996 Fiscal Year Final Research Report Summary
Wilms tumor suppressor gene WT1 blocks cell cycle progression
Project/Area Number |
07457580
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Pathological medical chemistry
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Research Institution | Osaka 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
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Keywords | tumor 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.
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[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)
Description
「研究成果報告書概要(欧文)」より
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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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「研究成果報告書概要(欧文)」より
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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)
Description
「研究成果報告書概要(欧文)」より
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