Bisphenol AF-induced endogenous transcription is mediated by ERα and ERK1/2 activation in human breast cancer cells.

Abstract

Bisphenol AF (BPAF)-induced transcriptional activity has been evaluated by luciferase reporter assay. However, the molecular mechanism of BPAF-induced endogenous transcription in human breast cancer cells has not been fully elucidated. In the present study, we investigated the effect and mechanism of BPAF-induced endogenous transcription detected by real-time PCR in human breast cancer cells. We found that BPAF stimulated transcription of estrogen responsive genes, such as trefoil factor 1 (TFF1), growth regulation by estrogen in breast cancer 1 (GREB1) and cathepsin D (CTSD), through dose-dependent and time-dependent manners in T47D and MCF7 cells. Gene-silencing of ERα, ERβ and G protein-coupled estrogen receptor 1 (GPER) by small interfering RNA revealed that BPAF-induced endogenous transcription was dependent on ERα and GPER, implying both genomic and nongenomic pathways might be involved in the endogenous transcription induced by BPAF. ERα-mediated gene transcription was further confirmed by inhibition of ER activity using ICI 182780 in ERα-positive T47D and MCF7 cells as well as overexpression of ERα in ERα-negative MDA-MB-231 breast cancer cells. Moreover, we utilized Src tyrosine kinase inhibitor PP2 and two MEK inhibitors PD98059 and U0126 to elucidate the rapid nongenomic activation of Src/MEK/ERK1/2 cascade on endogenous transcription. Our data showed that BPAF-induced transcription could be significantly blocked by PP2, PD98059 and U0126, suggesting activation of ERK1/2 was also required to regulate endogenous transcription. Taken together, these results indicate that BPAF-induced endogenous transcription of estrogen responsive genes is mediated through both genomic and nongenomic pathways involving the ERα and ERK1/2 activation in human breast cancer cells.

• Authors: Ming Li, Jing Guo, Wenhui Gao, Jianlong Yu, Xiaoyu Han, Jing Zhang, Bing Shao
• Journal: PloS one (PLoS One) Vol. 9 Issue 4 Pg. e94725 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24727858 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzhydryl Compounds
• Estrogen Receptor alpha
• GPER1 protein, human
• Phenols
• Receptors, Estrogen
• Receptors, G-Protein-Coupled
• Proto-Oncogene Proteins B-raf
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• 4,4'-hexafluorisopropylidene diphenol

Topics

• Benzhydryl Compounds (pharmacology)
• Breast Neoplasms (genetics, metabolism)
• Cell Line, Tumor
• Enzyme Activation
• Estrogen Receptor alpha (metabolism)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Phenols (pharmacology)
• Proto-Oncogene Proteins B-raf (metabolism)
• Receptors, Estrogen (metabolism)
• Receptors, G-Protein-Coupled (metabolism)
• Transcription, Genetic