Endocrine Abstracts

Epithelial–mesenchymal transition (EMT) is an important process appeared in tumour migration or progression, which is activated by 17β-estradiol (E₂). As a typical endocrine disrupting chemical (EDC), bisphenol A (BPA) has a potential to promote EMT and migration of oestrogen responsive cancers. On the contrary, genistein (GEN) as a phytoestrogen is known to have chemopreventive effects in diverse cancers. In the present study, the effects of BPA and GEN on EMT and migration of BG-1 ovarian cancer cells and the underlying mechanism were investigated. ICI 182,780, an oestrogen receptor (ER) antagonist, was co-treated with E₂ or BPA to BG-1 cells to identify the relevance of ER signalling in EMT and migration. As results, E₂ and BPA upregulated the protein expression of vimentin, cathepsin D, and MMP-2, but downregulated the protein expression of E-cadherin via ER signalling, suggesting that E₂ and BPA promoted EMT and cell migration related gene expressions. However, the increased protein expression of Vimentin, Cathepsin D, and MMP-2 by E₂ or BPA was reduced by the co-treatment of GEN. In a scratch assay, the migration capability of BG-1 cells was enhanced by E₂ and BPA via ER signalling pathway, but reversed by the co-treatment of GEN. In the protein expression of SnoN and Smad3, E₂ and BPA upregulated SnoN, a negative regulator of TGF-β signalling, and downregulated Smad3, a transcription factor in the downstream pathway of TGF-β signalling, suggesting that E₂ and BPA simultaneously lead the downregulation of TGF-β signalling in the process of induction of EMT and migration of BG-1 cells via ER signalling. On the other hand, the co-treatment of GEN reversed the downregulation of TGF-β signalling by E₂ and BPA. Taken together, GEN suppressed EMT and migration capacities of BG-1 ovarian cancer cells enhanced by E₂ and BPA via ER signalling and the downregulation of TGF-β signalling.

Disclosure: This work was also supported by a grant from the Next-Generation BioGreen 21 Program (no. PJ009599), Rural Development Administration, Republic of Korea.