Suppression of apoptosis following hormone-retractory prostate cancer.

1999 Fiscal Year Final Research Report Summary

• Project/Area Number: 10671460
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: The University of Tokyo
• Principal Investigator: TAKEUCHI Takumi The Univ. of Tokyo, Dept. of Urol, Associate Professor, 医学部・付属病院, 講師 (90167487)
• 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)
• Project Period (FY): 1998 – 1999
• Keywords: Prostate / Apoptosis / ICE

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.