The Roles of Human Sucrose Nonfermenting Protein 2 Homologue in the Tumor-Promoting Functions of Rsf-1.

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题名:	The Roles of Human Sucrose Nonfermenting Protein 2 Homologue in the Tumor-Promoting Functions of Rsf-1.
作者:	許晉銓(Jinn-Chyuan Sheu);(Jung Hye Choi);(Isil Yyldyz);蔡輔仁(Fuu-Jen Tsai);(Yosef Shaul);(Tian-Li Wang);(Ie-Ming Shih)*
贡献者:	中醫學院中國醫學研究所;中國附醫醫學研究部遺傳中心
关键词:	ovarian cancer;Gynecologic cancers: ovarian;Gene Expression, Chromatin Regulation, and Ongogenomics;Tumor promotion and progression
日期:	2008-06
上传时间:	2009-08-20 17:48:17 (UTC+8)
摘要:	Rsf-1 interacts with human sucrose nonfermenting protein 2 homologue (hSNF2H) to form a chromatin remodeling complex that participates in several biological processes. We have previously shown that Rsf-1 gene amplification was associated with the most aggressive type of ovarian cancer and cancer cells with Rsf-1 overexpression depended on Rsf-1 to survive. In this report, we determine if formation of the Rsf-1/hSNF2H complex could be one of the mechanisms contributing to tumor cell survival and growth in ovarian carcinomas. Based on immunohistochemistry, we found that Rsf-1 and hSNF2H were co-upregulated in ovarian cancer tissues. Ectopic expression of Rsf-1 in SKOV3 ovarian cancer cells with undetectable endogenous Rsf-1 expression enhanced hSNF2H protein levels and promoted SKOV3 tumor growth in a mouse xenograft model. Our studies also indicated that induction of Rsf-1 expression affected the molecular partnership of hSNF2H and translocated hSNF2H into nuclei where it colocalized with Rsf-1. Furthermore, analysis of Rsf-1 deletion mutants showed that the Rsf-D4 fragment contained the hSNF2H binding site based on coimmunoprecipitation and in vitro competition assays. As compared with other truncated mutants, expression of Rsf-D4 resulted in remarkable growth inhibition in ovarian cancer cells with Rsf-1 gene amplification and overexpression, but not in those without detectable Rsf-1 expression. The above findings suggest that interaction between Rsf-1 and hSNF2H may define a survival signal in those tumors overexpressing Rsf-1.
關聯:	CANCER RESEARCH 68(11):4050~4057
显示于类别:	[中國醫學研究所] 期刊論文

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