RB1CC1 activates RB1 pathway and inhibits proliferation and cologenic survival in human cancer.
RB1CC1 activates RB1 pathway and inhibits proliferation and cologenic survival in human cancer.
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DOI：
10.1371/journal.pone.0011404
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发表时间：
2010-06-30
期刊：
影响因子：
3.7
通讯作者：
Okabe H
中科院分区：
文献类型：
--
作者：
Chano T;Ikebuchi K;Ochi Y;Tameno H;Tomita Y;Jin Y;Inaji H;Ishitobi M;Teramoto K;Nishimura I;Minami K;Inoue H;Isono T;Saitoh M;Shimada T;Hisa Y;Okabe H
Rb1诱导的卷曲线圈1(RB1CC1，也称为FIP200)通过直接与RB1启动子上游(从起始ATG起)201bp的富含GC的区域结合，在增强RB1途径中发挥作用。在此，我们通过免疫沉淀和免疫荧光实验确定了hSNF5和P53为RB1CC1的结合伙伴。通过染色质免疫沉淀、荧光素酶报告、逆转录聚合酶链式反应和免疫印迹分析这些分子与RB1通路的相互作用。用流式细胞仪或细胞生长实验检测RB1CC1对肿瘤生长的抑制作用。含有hSNF5和/或p53的核RB1CC1复合体激活了RB1、p16和p21的转录，并抑制了肿瘤细胞的生长。此外，乳腺癌组织中RB1CC1的核表达与RB1和p16的表达显著相关，Ki-67增殖指数与p53和RB1CC1的表达呈正相关。本研究表明，RB1CC1与hSNF5和/或p53一起通过转录激活RB1、p16和p21来增强RB1通路。RB1CC1的表达结合RB1和P53的表达状态有望为乳腺癌的临床实践和未来的治疗策略提供有用的信息。
RB1-inducible coiled-coil 1 (RB1CC1, also known as FIP200) plays a role in the enhancement of the RB1 pathway through the direct binding to a GC-rich region 201bp upstream (from the initiation ATG) of the RB1 promoter. Here, we identified hSNF5 and p53 as the binding partners of RB1CC1 by immunoprecipitation and immunofluorescence assays. Interaction between these molecules and the RB1 pathway was analyzed by the assays of chromatin immunoprecipitation, luciferase-reporter, reverse transcription-polymerase chain reaction and immunoblot. The tumor growth suppression by RB1CC1 was evaluated by flow cytometry or by a cell growth assay. The nuclear RB1CC1 complex involving hSNF5 and/or p53 activated transcription of RB1, p16 and p21, and suppressed tumor cell growth. Furthermore, nuclear RB1CC1 expression significantly correlated with those of RB1 and p16 in breast cancer tissue in vivo, and the Ki-67 proliferation index was dependent on p53 as well as RB1CC1. The present study indicates that RB1CC1 together with hSNF5 and/or p53 enhances the RB1 pathway through transcriptional activation of RB1, p16 and p21. Evaluation of RB1CC1 expression combined with RB1 and p53 status is expected to provide useful information in clinical practice and future therapeutic strategies in breast cancer.
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