Rsf-1, a chromatin remodelling protein, interacts with cyclin E1 and promotes tumour development

被引:33
作者
Sheu, Jim Jinn-Chyuan [1 ,2 ,3 ,4 ]
Choi, Jung Hye [1 ,5 ]
Guan, Bin [1 ]
Tsai, Fuu-Jen [2 ,3 ]
Hua, Chun-Hung [6 ]
Lai, Ming-Tsung [7 ,8 ]
Wang, Tian-Li [1 ]
Shih, Ie-Ming [1 ]
机构
[1] Johns Hopkins Med Inst, Dept Pathol Gynecol & Obstet & Oncol, Baltimore, MD 21231 USA
[2] China Med Univ Hosp, Ctr Human Genet, Taichung 40447, Taiwan
[3] China Med Univ, Sch Chinese Med, Taichung 40447, Taiwan
[4] Asia Univ, Dept Hlth & Nutr Biotechnol, Taichung 41354, Taiwan
[5] Kyung Hee Univ, Dept Oriental Pharm, Seoul 130701, South Korea
[6] China Med Univ Hosp, Dept Otolaryngol, Taichung 40447, Taiwan
[7] Chung Shan Med Univ Hosp, Dept Pathol, Taichung 40201, Taiwan
[8] Chung Shan Med Univ, Sch Med, Taichung 40201, Taiwan
关键词
Rsf-1; HBXAP; cyclin E1; chromatin remodelling; TP53mut; cancer development; TUBAL INTRAEPITHELIAL CARCINOMA; OVARIAN-CANCER; GENE AMPLIFICATION; FUNCTIONAL-ANALYSIS; DOWNSTREAM TARGET; POOR SURVIVAL; C-MYC; EXPRESSION; MUTATIONS; OVEREXPRESSION;
D O I
10.1002/path.4147
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Chromosome 11q13.5 containing RSF1 (HBXAP), a gene involved in chromatin remodelling, is amplified in several human cancers including ovarian carcinoma. Our previous studies demonstrated requirement of Rsf-1 for cell survival in cancer cells, which contributed to tumour progression; however, its role in tumourigenesis has not yet been elucidated. In this study, we co-immunoprecipitated proteins with Rsf-1 followed by nanoelectrospray mass spectrometry and identified cyclin E1, besides SNF2H, as one of the major Rsf-1 interacting proteins. Like RSF1, CCNE1 is frequently amplified in ovarian cancer, and both Rsf-1 and cyclin E1 were found co-up-regulated in ovarian cancer tissues. Ectopic expression of Rsf-1 and cyclin E1 in non-tumourigenic TP53mut RK3E cells led to an increase in cellular proliferation and tumour formation by activating cyclin E1-associated kinase (CDK2). Tumourigenesis was not detected if either cyclin E1 or Rsf-1 was expressed, or they were expressed in a TP53wt background. Domain mapping showed that cyclin E1 interacted with the first 441 amino acids of Rsf-1. Ectopic expression of this truncated domain significantly suppressed G1/S-phase transition, cellular proliferation, and tumour formation of RK3E-p53R175H/Rsf-1/cyclin E1 cells. The above findings suggest that Rsf-1 interacts and collaborates with cyclin E1 in neoplastic transformation and TP53 mutations are a prerequisite for tumour-promoting functions of the RSF/cyclin E1 complex.
引用
收藏
页码:559 / 568
页数:10
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