Docquier, A., Harmand, P. O., Fritsch, S., Chanrion, M., Darbon, J. M., Cavailles, V. (June 2010) The transcriptional coregulator RIP140 represses E2F1 activity and discriminates breast cancer subtypes. Clinical Cancer Research, 16 (11). pp. 2959-2970.
Abstract
Purpose: Receptor-interacting protein of 140 kDa (RIP140) is a transcriptional cofactor for nuclear receptors involved in reproduction and energy homeostasis. Our aim was to investigate its role in the regulation of E2F1 activity and target genes both in breast cancer cell lines and in tumor biopsies. Experimental Design: Glutathione S-transferase pull-down assays, coimmunoprecipitation experiments, and chromatin immunoprecipitation analysis were used to evidence interaction between RIP140 and E2F1. The effects of RIP140 expression on E2F1 activity were determined using transient transfection and quantification of E2F target mRNAs by quantitative real-time PCR. The effect on cell cycle was assessed by fluorescence-activated cell sorting analysis on cells overexpressing green fluorescent protein-tagged RIP140. A tumor microarray data set was used to investigate the expression of RIP140 and E2F1 target genes in 170 breast cancer patients. Results: We first evidenced the complex interaction between RIP140 and E2F1 and showed that RIP140 represses E2F1 transactivation on various transiently transfected E2F target promoters and inhibits the expression of several E2F1 target genes (such as CCNE1 and CCNB2). In agreement with a role for RIP140 in the control of E2F activity, we show that increasing RIP140 levels results in a reduction in the proportion of cells in S phase in various human cell lines. Finally, analysis of human breast cancers shows that low RIP140 mRNA expression was associated with high E2F1 target gene levels and basal-like tumors. Conclusion: This study shows that RIP140 is a regulator of the E2F pathway, which discriminates luminal- and basal-like tumors, emphasizing the importance of these regulations for a clinical cancer phenotype. ©2010 AACR.
| Item Type: | Paper |
|---|---|
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription bioinformatics > genomics and proteomics > analysis and processing > microarray gene expression processing diseases & disorders > cancer > cancer types > breast cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > green fluorescent protein |
| CSHL Authors: | |
| Communities: | CSHL labs > Powers lab |
| Depositing User: | CSHL Librarian |
| Date: | June 2010 |
| Date Deposited: | 29 Sep 2011 20:06 |
| Last Modified: | 02 Mar 2018 15:48 |
| PMCID: | PMC3112174 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/15401 |
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