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.

中文翻译：

---

CtBP1反式激活RAD51，赋予顺铂对乳腺癌细胞的抗性。

RAD51的过表达在包括乳腺癌在内的许多癌症中均被发现，并且与生存率低下有关。与正常细胞相比，RAD51启动子在癌细胞中活跃，表明RAD51被转录激活。但是，有关RAD51转录调控的机制和因素知之甚少。转录共抑制因子C末端结合蛋白1（CtBP1）是一种癌基因，可抑制一组肿瘤抑制因子的转录，这有助于癌症的发展。在这项研究中，免疫组化（IHC）显示在乳腺癌患者组织中RAD51表达与CtBP1表达呈正相关。短发夹RNA介导的CtBP1耗竭，染色质免疫沉淀和双重荧光素酶报告基因检测表明，CtBP1激活了乳腺癌细胞中RAD51的转录。CtBP1的耗竭增加了乳腺癌细胞对顺铂的敏感性，而CtBP1耗竭的乳腺癌细胞中外源RAD51的表达增加了对顺铂的抗性。结果表明，CtBP1通过RAD51的转录激活赋予乳腺癌细胞对顺铂耐药性。