title: Bisphenol A exerts estrogenic effects by modulating CDK1/2 and p38 MAP kinase activity.
abstract: Bisphenol A (BPA) is considered to be an endocrine disruptor, but the mechanisms by which it disrupts endocrine functions are poorly understood. Here, we have shown that BPA binds both estrogen receptor (ER)-α and ER-beta (ER-β) using a fluorescence polarization competitive binding assay. In addition, we found that BPA induced cell proliferation by modulating cell cycle-related genes in the MCF-7 human mammary cancer cell line. Moreover, using a BG1 luciferase ER transactivation assay, we found that BPA has estrogenic activity. Modulating the MAPK pathway by using an ERK inhibitor (PD98059) or a JNK inhibitor (SP600125) had no effect on the ability of BPA to induce estrogenic activity. However, the antiestrogen, ICI 182,780, and the p38 inhibitor, PD 169316 successfully blocked BPA-induced estrogenic activity. Our findings suggest that BPA mimics ER-dependent estrogenic activity by targeting proteins that regulate the cell cycle and p38 MAPK.
authors.affiliation: a Food Safety Risk Assessment Division , National Institute of Food and Drug Safety Evaluation , Chungcheongbuk-do , Korea.
authors.forename: Hee-Seok
authors.initials: HS
authors.lastname: Lee
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Park
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Oh
authors.forename: Guiim
authors.initials: G
authors.lastname: Moon
authors.forename: Myung-Sil
authors.initials: MS
authors.lastname: Hwang
authors.forename: Sang-Yub
authors.initials: SY
authors.lastname: Kim
authors.forename: Min-Ki
authors.initials: MK
authors.lastname: Shin
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Koh
authors.forename: Jin-Hyang
authors.initials: JH
authors.lastname: Suh
authors.forename: Hui-Seung
authors.initials: HS
authors.lastname: Kang
authors.forename: Ju-Hong
authors.initials: JH
authors.lastname: Jeon
authors.forename: Gyu-Seek
authors.initials: GS
authors.lastname: Rhee
authors.forename: Jin-Hwan
authors.initials: JH
authors.lastname: Hong
mesh_terms: D001559:Benzhydryl Compounds / Q000378:metabolism / Q000494:pharmacology*; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D010636:Phenols / Q000378:metabolism / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D016203:CDC2 Protein Kinase; D051357:Cyclin-Dependent Kinase 2; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D010636:Phenols; D048051:p38 Mitogen-Activated Protein Kinases; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: CDK1/2; Endocrine disruptors; bisphenol A; estrogenic activity; p38 MAPK