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.
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Authors | Yu Deng, Wanjun Guo, Ning Xu, Fulun Li, Jian Li |
Journal | Molecular carcinogenesis
(Mol Carcinog)
Vol. 59
Issue 5
Pg. 512-519
(05 2020)
ISSN: 1098-2744 [Electronic] United States |
PMID | 32124501
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2020 Wiley Periodicals, Inc. |
Chemical References |
- Antineoplastic Agents
- Biomarkers, Tumor
- DNA-Binding Proteins
- Alcohol Oxidoreductases
- C-terminal binding protein
- RAD51 protein, human
- Rad51 Recombinase
- Cisplatin
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Topics |
- Alcohol Oxidoreductases
(genetics, metabolism)
- Antineoplastic Agents
(pharmacology)
- Apoptosis
- Biomarkers, Tumor
(genetics, metabolism)
- Breast Neoplasms
(drug therapy, genetics, metabolism, pathology)
- Cell Proliferation
- Cisplatin
(pharmacology)
- DNA-Binding Proteins
(genetics, metabolism)
- Drug Resistance, Neoplasm
(genetics)
- Female
- Gene Expression Regulation, Neoplastic
- Humans
- Prognosis
- Promoter Regions, Genetic
- Rad51 Recombinase
(genetics, metabolism)
- Transcriptional Activation
- Tumor Cells, Cultured
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