Molecular mechanism of action of bisphenol and bisphenol A mediated by oestrogen receptor alpha in growth and apoptosis of breast cancer cells.

ABSTRACT: Oestrogen receptor alpha (ER?) binds to different ligand which can function as complete/partial oestrogen-agonist or antagonist. This depends on the chemical structure of the ligands which modulates the transcriptional activity of the oestrogen-responsive genes by altering the conformation of the liganded-ER? complex. This study determined the molecular mechanism of oestrogen-agonistic/antagonistic action of structurally similar ligands, bisphenol (BP) and bisphenol A (BPA) on cell proliferation and apoptosis of ER? + ve breast cancer cells.DNA was measured to assess the proliferation and apoptosis of breast cancer cells. RT-PCR and ChIP assays were performed to quantify the transcripts of TFF1 gene and recruitment of ER? and SRC3 at the promoter of TFF1 gene respectively. Molecular docking was used to delineate the binding modes of BP and BPA with the ER?. PCR-based arrays were used to study the regulation of the apoptotic genes.BP and BPA induced the proliferation of breast cancer cells; however, unlike BPA, BP failed to induce apoptosis. BPA consistently acted as an agonist in our studies but BP exhibited mixed agonistic/antagonistic properties. Molecular docking revealed agonistic and antagonistic mode of binding for BPA and BP respectively. BPA treatment resembled E2 treatment in terms of PCR-based regulation of apoptotic genes whereas BP was similar to 4OHT treatment.The chemical structure of ER? ligand determines the agonistic or antagonistic biological responses by the virtue of their binding mode, conformation of the liganded-ER? complex and the context of the cellular function.

SUBMITTER: Sengupta S 

PROVIDER: S-EPMC3632247 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature