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.
Highlights
During the past two decades, bisphenol A (BPA) and its analogues have received growing concerns for their endocrine disrupting properties and ubiquitous occurrences [1,2]
Effect of Bisphenol AF (BPAF) on endogenous transcription of estrogen responsive genes To evaluate the effect of BPAF on endogenous transcription, we conducted the real-time PCR to detect mRNA levels of estrogen responsive genes, such as trefoil factor 1 (TFF1), GREB1 and cathepsin D (CTSD) in ERapositive T47D and MCF7 breast cancer cell lines and ERanegative MDA-MB-231 breast cancer cell line
We investigated BPAF-induced endogenous transcription of estrogen responsive genes in human breast cancer cells
Summary
During the past two decades, bisphenol A (BPA) and its analogues have received growing concerns for their endocrine disrupting properties and ubiquitous occurrences [1,2]. Bisphenol AF (BPAF) is a bisphenol analogue of BPA and primarily used as a monomer for polyimides, polyamides, polyesters and other specialty polymers and as a cross linker for certain fluoroelastomers [3]. It has been reported that BPAF is extensively occurred in the river, sediment and soil after released into the ambient environment around a manufacturing plant in China [5]. BPAF strongly binds to both ERa and ERb as detected by radioligand binding assay. The receptorbinding activity of BPAF is about three times more potent for ERb than for ERa [8]. Luciferase reporter assay indicates that BPAF is a full agonist for ERa, but displays little potency to activating ERb
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