Suppression of apoptosis following hormone-retractory prostate cancer.
| Project/Area Number |
10671460
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TAKEUCHI Takumi (1999) The Univ. of Tokyo, Dept. of Urol, Associate Professor, 医学部・付属病院, 講師 (90167487)
植木 哲雄 (1998) 東京大学, 医学部附属病院, 助手 (60184917)
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| Co-Investigator(Kenkyū-buntansha) |
YAMASAKI Satoru The Univ. of Tokyo, Dept. of Urol, Consultant, 医学部・付属病院, 助手 (60282654)
MORIYAMA Nobuo The Univ. of Tokyo, Dept. of Urol, Associate Professor, 医学部・付属病院, 講師 (80143501)
佐山 孝 東京大学, 医学部・附属病院, 助手 (90187287)
田中 良典 東京大学, 医学部・附属病院, 助手 (50236650)
田島 惇 東京大学, 医学部・附属病院, 助教授 (10111808)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Prostate / Apoptosis / ICE / 腎細胞癌 |
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| Research Abstract |
Renal cell cancer is a unique solid tumor which occasionally shows spontaneous regression even at an advanced stage, of which underlying mechanism is not well understood. To investigate a potential role of a pro-apoptotic molecule caspase-1 in the growth regulation of renal cell cancer, we created transfectants expressing exogenous caspase-1 from a murine renal cancer cell line Renca Overexpression of caspase-1 did not affect growth of Renca cells in vitro at their exponential phase, but induced apoptotic cell death at 50-75% confluence, while control bells underwent apoptosis only after reaching 100% confluence. When implanted to the flank of a syngeneic BALB/c mouse, caspase-1 overexpressing Renca cells did not effectively establish growth as a solid tumor, forming a measurable tumor in only 7 of 11 (41%) animals, while control cells formed a tumor in 6 of 6 (100%) animals. The growth of tumors from caspase-1 overexpressing cells markedly slowed down after reaching 5-10 mm in diameter, and histological examination of such tumors revealed numerous apoptotic cells positively stained by TUNEL assay. Interestingly, endogenous caspase-1 was not detected in the tumors from control cells, which re-expressed caspase-1 when re-cultured and exposed to a demethylation reagent 5-aza-2'-deoxycytidine. Furthermore, treatment of a human renal cancer dell line ACHN with 5-aza-2'-deoxycytidine also recovered caspase-1 expression, which was not detected before treatment. These data suggest that silencing of caspase-1 through DNA methylation may be involved in the oncogenesis of some renal cell cancers growing as a solid tumor.
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Report
(3 results)
Research Products
(1 results)
