CtBP1 transactivates RAD51 and confers cisplatin resistance to breast cancer cells. Issue 5 (2nd March 2020)

• Record Type: Journal Article
• Authors: Deng, Yu; Guo, Wanjun; Xu, Ning; Li, Fulun; Li, Jian
• Is Part Of: Molecular carcinogenesis. Volume 59:Issue 5(2020)
• Page Start: 512
• Page End: 519
• Publication Date: 2020-03-02
• Subjects: cisplatin -- C‐terminal binding protein 1 -- DNA repair -- drug resistance; Carcinogenesis -- Molecular aspects -- Periodicals; 616.994071
• DOI: 10.1002/mc.23175
• Languages: English
• ISSNs: 0899-1987

Abstract

Abstract: Overexpression of RAD51 is found in many cancers including breast cancer and is associated with poor survival. Compared with normal cells, RAD51 promoter is hyperactive in cancer cells indicating that RAD51 is transcriptionally activated. However, little is known about the mechanisms and factors involved in RAD51 transcription regulation. Transcription corepressor, C‐terminal binding protein 1 (CtBP1), is an oncogene repressing a panel of tumor suppressors transcription, which contributes to cancer progression. In this study, immunohistochemistry (IHC) revealed that RAD51 expression was positively correlated with CtBP1 expression in breast cancer patient tissues; short hairpin RNA‐mediated CtBP1 depletion, chromatin immunoprecipitation, and dual‐luciferase reporter assays showed that CtBP1 activated RAD51 transcription in breast cancer cells. Depletion of CtBP1 increased breast cancer cells' sensitivity to cisplatin and, in turn, expression of exogenous RAD51 in the CtBP1‐depleted breast cancer cells increased resistance to cisplatin. The results demonstrated that CtBP1 conferred breast cancer cells resistance to cisplatin through transcriptional activation of RAD51.