The roles of human sucrose nonfermenting protein 2 homologue in the tumor-promoting functions of Rsf-1.
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.
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA.
Jim Jinn-Chyuan
JJ
Sheu
Jung Hye
JH
Choi
Isil
I
Yildiz
Fuu-Jen
FJ
Tsai
Yosef
Y
Shaul
Tian-Li
TL
Wang
Ie-Ming
IeM
Shih
D000251:Adenosine Triphosphatases / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D002460:Cell Line; D002843:Chromatin / Q000502:physiology; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism / Q000502:physiology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008819:Mice, Nude; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000473:pathology; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*
D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; C452851:RSF1 protein, human; D015534:Trans-Activators; D000251:Adenosine Triphosphatases; C409462:SMARCA5 protein, human