Bisphenol A regulates Snail-mediated epithelial-mesenchymal transition in hemangioma cells.

Abstract

Hemangioma (HA) can be exposed to bisphenol A (BPA) through direct skin absorption. Although numerous studies indicated that BPA can trigger the progression of cancers, there is no study concerning the effects of BPA on development of HA. Our present study revealed that nanomolar BPA can significantly increase the in vitro migration and invasion of HA cells via induction of epithelial-mesenchymal transition (EMT), which was evidenced by the upregulation of vimentin and downregulation of E-cadherin. The BPA treatment also significantly increased the expression and nuclear localization of Snail and the key transcription factor of EMT, while it had no effect on the expression of other transcription factors such as Slug, Twist, or ZEB1. Silencing of Snail by small interfering RNAs attenuated BPA-induced downregulation of cadherin and upregulation of vimentin, suggesting that Snail is essential for BPA-induced EMT. Both estrogen receptor α (ERα) and G protein-coupled estrogen receptor (GPER) were expressed in HA cells; furthermore, BPA treatment can increase the expression of both ERα and GPER. However, only the inhibitor of ERα (ICI 182, 780), and not GPER (G15), can abolish BPA-induced upregulation of Snail. It suggested that ERα is involved in BPA-induced EMT of HA cells. Collectively, our data suggested that BPA can trigger the EMT of HA cells via ERα/Snail signals. It indicated that more attention should be paid to the skin exposure to BPA for HA patients.