Bisphenol A exerts estrogenic effects by modulating CDK1/2 and p38 MAP kinase activity. Issue 8 (3rd August 2014)

• Record Type: Journal Article
• Authors: Lee, Hee-Seok; Park, Eun-Jung; Oh, Jae-Ho; Moon, Guiim; Hwang, Myung-Sil; Kim, Sang-Yub; Shin, Min-Ki; Koh, Young-Ho; Suh, Jin-Hyang; Kang, Hui-Seung; Jeon, Ju-Hong; Rhee, Gyu-Seek; Hong, Jin-Hwan
• Is Part Of: Bioscience, biotechnology, and biochemistry. Volume 78:Issue 8(2014)
• Page Start: 1371
• Page End: 1375
• Publication Date: 2014-08-03
• Subjects: Endocrine disruptors -- bisphenol A -- estrogenic activity -- CDK1/2 -- p38 MAPK; Biotechnology -- Periodicals; Biochemistry -- Periodicals; 660.6
• DOI: 10.1080/09168451.2014.921557
• Languages: English
• ISSNs: 0916-8451

Abstract

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. Graphical abstract: : Bisphenol A exerts estrogen receptor–dependent estrogenic activity by targeting proteins that regulate the cell cycle and p38 MAPK.