title: Low doses of bisphenol A stimulate the proliferation of breast cancer cells via ERK1/2/ERRγ signals.
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.
authors.affiliation: School of Biomedicine Sciences, Chengdu Medical College, Chengdu, China.
authors.forename: Haixing
authors.initials: H
authors.lastname: Song
authors.affiliation: School of Biomedicine Sciences, Chengdu Medical College, Chengdu, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: School of Basic Medical Sciences, Chengdu Medical College, Chengdu, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.affiliation: Center of Science and Research, Chengdu Medical College, Chengdu, China.
authors.forename: Minhui
authors.initials: M
authors.lastname: Li
authors.affiliation: School of Biomedicine Sciences, Chengdu Medical College, Chengdu, China.
authors.forename: Yuhan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: School of Biomedicine Sciences, Chengdu Medical College, Chengdu, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Du
authors.affiliation: School of Biomedicine Sciences, Chengdu Medical College, Chengdu, China. Electronic address: pankejian2005@163.com.
authors.forename: Kejian
authors.initials: K
authors.lastname: Pan
authors.affiliation: School of Biomedicine Sciences, Chengdu Medical College, Chengdu, China. Electronic address: zhangkunyyo@163.com.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
mesh_terms: D021581:Active Transport, Cell Nucleus; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000502:physiology; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D061986:MCF-7 Cells; D010636:Phenols / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D015398:Signal Transduction; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D047628:Estrogen Receptor alpha; D010636:Phenols; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; C506487:ESR1 protein, human; C490917:ESRRG protein, human; C109584:GPER1 protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: BPA; Breast cancer; ERK1/2; ERRγ; Proliferation