This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sheu, J. J.-C. Articles by Shih, I.-M. Search for Related Content PubMed PubMed Citation Articles by Sheu, J. J.-C. Articles by Shih, I.-M.

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

¹ Departments of Pathology, Oncology, and Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, Maryland; ² Human Genetic Center, China Medical University Hospital and Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan; and ³ Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel

Requests for reprints: Ie-Ming Shih, Department of Pathology, Johns Hopkins University, 1550 Orleans Street, Room 305, Baltimore, MD 21231. Phone: 410-502-7774; E-mail: ishih{at}jhmi.edu.

Key Words: ovarian cancer • Gynecologic cancers: ovarian • Gene Expression, Chromatin Regulation, and Ongogenomics • Tumor promotion and progression

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. [Cancer Res 2008;68(11):4050–7]

This article has been cited by other articles:

				J. H. Choi, J. J.-C. Sheu, B. Guan, N. Jinawath, P. Markowski, T.-L. Wang, and I.-M. Shih Functional Analysis of 11q13.5 Amplicon Identifies Rsf-1 (HBXAP) as a Gene Involved in Paclitaxel Resistance in Ovarian Cancer Cancer Res., February 15, 2009; 69(4): 1407 - 1415. [Abstract] [Full Text] [PDF]