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.