2001 Fiscal Year Final Research Report Summary
Molecular mechanism of endometrial carcinoma development and their application for the new molecular target therapy
| Project/Area Number |
12470344
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Kyushu University |
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Principal Investigator |
WAKE Norio Medical Institute of Bioregulation, Kyushu Univ., Professor, 生体防御医学研究所, 教授 (50158606)
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| Co-Investigator(Kenkyū-buntansha) |
ARIMA Takahiro Medical Institute of Bioregulation, Kyushu Univ., Research Associate, 生体防御医学研究所, 助手 (80253532)
KATO Kiyoko Medical Institute of Bioregulation, Kyushu Univ., Assistant Professor, 生体防御医学研究所, 講師 (10253527)
KATO Hidenori Medical Institute of Bioregulation, Kyushu Univ., Assistant Professor, 生体防御医学研究所, 講師 (60214392)
MATSUDA Takao Medical Institute of Bioregulation, Kyushu Univ., Research Associate, 生体防御医学研究所, 助手 (10304825)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Endometrial cancer / tumor suppressor gene / chromosome 1q42 / Ras / ERα / p53 / Cell senescence / MDM2 |
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| Research Abstract |
1. We have identified the 1q42 region as an endometrial cancer suppressor gene locus. Three kinds of genes (ORF12, HUBCEP 70 and ENST27746) are involved in this region. Now, we are investigating the tumor suppressor function of these genes by the transfection into endometrial cancer cell lines.
2.
a. Both K-and H-Ras mediated proliferative signals in Rat endometrial cells(RENT4). However, K-Ras elicited the apoptosis through activating MAPK and in turn, H-Ras protected RENT4 from apoptosis. The data suggest that each Ras protein has distint function.
b. ERα functions downstream of K-Ras. Expression of activated [12Val] K-Ras resulted in the NIH3T3 cell (K12V cells) transformation through activating ERα activity as a transcription factor. Dominant-negative ERα expression in K12V cells resulted in cell growth suppression and subsequent cell senescence induction. p21 upregulation through DNERα-MDM2-p53 signalling corresponded this cell senescence induction. ERα expression in NIH3T3 cells contributed to the upregulation of MDM2 through c-Jun. These data implicate the signalling from ERα to p53, regulating cell senescence in NIH3T3 cells.
c. NaB(Sodium Butyrate) elicited G0/G1 arrest and subsequent senescence through p53-independent p21 upregulation in endometrial and ovarian cancer with intact pRb protein. In contrast, NaB arrested cervical cancer cells with pRb both at G0/G1 and G2/M phase and induced cell senescence. ECM and its receptors upregulated in senescence cancer cells in response to NaB.
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Research Products
(12 results)
