Low doses of bisphenol A stimulate the proliferation of breast cancer cells via ERK1/2/ERRγ signals. Issue 1 (25th December 2015)

• Record Type: Journal Article
• Authors: Song, Haixing; Zhang, Tao; Yang, Ping; Li, Minhui; Yang, Yuhan; Wang, Yuanyuan; Du, Jun; Pan, Kejian; Zhang, Kun
• Is Part Of: Toxicology in vitro. Volume 30:Issue 1 Part B(2015)
• Page Start: 521
• Page End: 528
• Publication Date: 2015-12-25
• Subjects: BPA -- ERRγ -- ERK1/2 -- Breast cancer -- Proliferation; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2015.09.009
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: The effects and mechanisms of bisphenol A (BPA) on the development of breast cancer are still not well illustrated. The present study revealed that nanomolar BPA significantly promoted the proliferation of both estrogen receptor (ER) positive (MCF-7) and negative (SkBr3) breast cancer cells, which was confirmed by up regulation of proliferating cell nuclear antigen (PCNA) and Bcl-2. Neither ERα nor G-protein-coupled estrogen receptor (GPER) mediated this effect of BPA because their inhibitors had no effect on the BPA induced cell proliferation. However, silencing of estrogen related receptor gamma (ERRγ) by its specific siRNA significantly abolished BPA induced proliferation of breast cancer cells, while si-ERRα had no similar effect. Moreover, nanomolar BPA up regulated the mRNA and protein levels of ERRγ and triggered its nuclear translocation via a time dependent manner. Further studies revealed that 10 − 8 M BPA obviously increased the phosphorylation of ERK1/2, while had no similar effect on the phosphorylation of JNK and p38 MAPK. Further, PD 98059, the inhibitor of ERK1/2, significantly abolished the BPA induced up regulation of ERRγ and proliferation of breast cancer cells. Collectively, our results revealed that nanomolar BPA can trigger the proliferation of breast cancer cells via ERK1/2/ERRγ signals. Given that nanomolar BPA has been widely detected in human tissues, the clinical relevance of BPA and breast cancer progression should be further investigated. Highlights: Nanomolar BPA stimulated the proliferation of both ER positive and negative breast cancer cells. Neither ERα nor GPER mediated the BPA-induced proliferation. Silencing of ERRγ significantly abolished the BPA-induced proliferation. BPA stimulated the expression and nuclear localization of ERRγ. ERK1/2 mediated the BPA induced-up regulation of ERRγ and cell proliferation.