Bisphenol A induces human uterine leiomyoma cell proliferation through membrane-associated ERα36 via nongenomic signaling pathways. (15th March 2019)

• Record Type: Journal Article
• Authors: Yu, Linda; Das, Parikshit; Vall, Alejandra J.; Yan, Yitang; Gao, Xioahua; Sifre, Maria I.; Bortner, Carl D.; Castro, Lysandra; Kissling, Grace E.; Moore, Alicia B.; Dixon, Darlene
• Is Part Of: Molecular and cellular endocrinology. Volume 484(2019)
• Page Start: 59
• Page End: 68
• Publication Date: 2019-03-15
• Subjects: Bisphenol A -- Leiomyoma cells -- Estrogen receptor alpha36 (ERα36) -- Nongenomic signaling; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2019.01.001
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: The role of ERα36 in regulating BPA's effects and its potential as a risk factor for human uterine fibroids were evaluated. BPA at low concentrations (10 −6 μM - 10 μM) increased proliferation by facilitating progression of hormonally regulated, immortalized human uterine leiomyoma (ht-UtLM; fibroid) cells from G0 -G1 into S phase of the cell cycle; whereas, higher concentrations (100 μM–200 μM) decreased growth. BPA upregulated ERα36 gene and protein expression, and induced increased SOS1 and Grb2 protein expression, both of which are mediators of the MAPKp44/42 /ERK1/2 pathway. EGFR (pEGFR), Ras, and MAPKp44/42 were phosphorylated with concurrent Src activation in ht-UtLM cells within 10 min of BPA exposure. BPA enhanced colocalization of phosphorylated Src (pSrc) to ERα36 and coimmunoprecipitation of pSrc with pEGFR. Silencing ERα36 with siERα36 abolished the above effects. BPA induced proliferation in ht-UtLM cells through membrane-associated ERα36 with activation of Src, EGFR, Ras, and MAPK nongenomic signaling pathways. Highlights: ERα36 regulates BPA's effects in human uterine fibroid (ht-UtLM) cells. BPA at low concentrations increased cell proliferation and cell cycle progression. BPA upregulated ERα36 gene and protein expression and induced mediators of MAPK. BPA enhanced colocalization of phosphorylated Src to ERα36. Silencing ERα36 abolished BPA-induced nongenomic signaling and cell proliferation.