| Project/Area Number |
11557119
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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 | 展開研究 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | University of Tokyo |
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Principal Investigator |
YANO Tetsu The University of Tokyo Hospital, Assistant Professor, 医学部・附属病院, 講師 (90251264)
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| Co-Investigator(Kenkyū-buntansha) |
TANUMA Seiichi Science University of Tokyo, Professor, 薬学部, 教授 (10142449)
OSUGA Yutaka The University of Tokyo Hospital, Assistant, 医学部・附属病院, 助手 (80260496)
MOMOEDA Mikio The University of Tokyo Hospital, Assistant, 医学部・附属病院, 助手 (50221627)
KIMURA Tatsuji Tonen Research Institute, Research Stuff, 総合研究所, 研究職員
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 2000: ¥6,000,000 (Direct Cost: ¥6,000,000)
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| Keywords | apoptosis / ovarian cancer / endometrial cancer / DNase / peptide analogs / GnRH analogs / 悪性腫瘍 / DNA断片化 |
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| Research Abstract |
RT-PCR revealed the expression of mRNA for GnRH and its receptor in human epithelial ovarian cancer cell lines (HTOA, OV-1063 and OVCAR-3) and human endometrial cancer cell lines (HEC-1 and HHUA). Furthermore, the expression of mRNA of DNaseγ and CAD (caspase 3-activated DNase) was also detected by RT-PCR in these cell lines. The GnRH agonist, buserelin, and the GnRH antagonist, cetrorelix, increased the incidence of apoptosis in cultured HTOA cells as determined by TUNEL staining. The treatment with both analogs suppressed the growth of xenografts of HTOA cell line in nude mice to the same extent. In cultured HTOA cells, the both GnRH analogs suppressed EGF-induced tyrosine phosphorylation of EGF receptor and blocked cell cycle progression in G0/G1 phase. These findings lead us to suggest that the antineoplastic actions of both GnRH analogs might be based on apoptosis induced by the activation of DNase, suppression of EGF-induced signaling pathway or cell cycle arrest at G1. On the other hand, in the five cell lines described above, the expression of DNaseγ protein could not be detected in these cell lines by Western blotting using anti-DNaseγ polyclonal and monoclonal antibodies generated by us previously. Then a remarkably specific anti-DNaseγ monoclonal antibody was newly generated. This antibody has been shown to be useful for Western blotting and ELISA.
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