Bisphenol S promotes the cell cycle progression and cell proliferation through ERα-cyclin D-CDK4/6-pRb pathway in MCF-7 breast cancer cells
| Autor: | Zhenxian Lin, Xiaona Zhang, Shaoguo Ru, Fei Zhao |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cyclin D Breast Neoplasms Endocrine Disruptors Toxicology Retinoblastoma Protein 03 medical and health sciences 0302 clinical medicine Cyclin D1 Phenols Humans Benzhydryl Compounds Phosphorylation Cell Proliferation Cyclin D/Cdk4 Pharmacology biology Chemistry Cell growth Estrogen Receptor alpha Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinase 5 Cell cycle G1 Phase Cell Cycle Checkpoints 030104 developmental biology Cyclin E2 030220 oncology & carcinogenesis MCF-7 Cells biology.protein Cancer research Female Cyclin-dependent kinase 6 hormones hormone substitutes and hormone antagonists Cyclin A2 Signal Transduction |
| Zdroj: | Toxicology and Applied Pharmacology. 366:75-82 |
| ISSN: | 0041-008X |
| DOI: | 10.1016/j.taap.2019.01.017 |
| Popis: | Bisphenol S (BPS), exhibiting estrogenic activity, has been reported to promote cell proliferation in MCF-7 breast cancer cells; however, the underlying mechanism remains unclear. In this study, BPS (1–100 μM) significantly promoted cell proliferation in ERα positive MCF-7 cells, but not in ERα negative MDA-MB-231 or SK-BR-3 cells, confirming the important role of ERα in BPS-induced cell proliferation. Results of the flow cytometry analysis indicated that 10 μM BPS promoted MCF-7 proliferation by accelerating G1 to S phase transition of the cell cycle. BPS increased cyclin D1 expression and phospho-retinoblastoma (p-Rb) levels, resulting in the release of E2F transcription factors and the increased expression of downstream cyclin E2 and cyclin A2 genes to promote the cell cycle progression. Moreover, BPS-induced Rb phosphorylation and cell cycle progression were prevented by the ERα inhibitor ICI 182,780 and methylpiperidino pyrazole, as well as cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitor PD 0332991, indicating that the underlying mechanisms involve ERα-dependent pathways but also mediated by cyclin D-CDK4/6. Overall, our result showed, for the first time, that BPS promoted cell cycle progression and cell proliferation through the ERα-cyclin D-CDK4/6-pRb pathway in MCF-7 breast cancer cells. This study provides a novel insight regarding the potential role of cyclin D-CDK4/6-pRb pathway in mediating the proliferative effects of BPS in breast cancer cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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