Endocrine disrupting chemicals (EDCs) have brougt the growing concern about the potential to interfere with the endocrine system and to cause health problems. Among EDCs, bisphenol A (BPA) and 1,1,1-trichloro-2,2-bis(4-methoxyphenol)-ethane (methoxychlor, MXC) can bind to estrogen receptors (ERs) and lead abnormality of ER depenent signaling pathways, resulting in human health problems such as dysfuction of reproduction and carcinogenesis. In this study, we investigated whether BPA and MXC promote transition of cell cycle and the cell growth by ER binding in human breast cancer cells, MCF-7 cells. We further examined the alterations of the cell cycle -related genes in MCF-7 cells following treatments with BPA or MXC, compared to a vehicle (EtOH). Both BPA and MXC induced up-regulation of cyclin D1 and down-regulation of p21. To determine whether BPA and MXC increase the growth of MCF-7 cells though an ER signaling pathway, we co-treated MCF-7 with agonists of ER signaling pathways (propyl pyrazoletriol, PPT, and diarylpropionitrile, DPN) or an antagonist of ER (ICI 182,780) in the presence of BPA or MXC. The effect of BPA and MXC on the breast cancer cell growth was enhanced in the presence of PPT in MCF-7 cells. The expressions of cyclin D1 and p21 were altered by BPA or MXC in the presence of PPT, but it was less altered by them in the presence of DPN. We knockdowned ERa gene expression via siRNA in MCF-7 cells before EDCs treatment. When the expression level of ERa was knockdowned in MCF-7 cells, effects of BPA and MXC were lost on the expression levels of cyclin D1 and p21 genes. Taken together, these results indicate that BPA and MXC altered the gene expressions associated with cell cycle, especially in G1/S transition, and resulted in the stimulation of breast cancer cell growth via an ERa signaling pathway. These collective results confirm that these EDCs may have the carcinogenicity via an ER-mediated signaling pathway in vitro. A futher study is required to determine whether EDCs may have a potency to be carcinogenic in human breast cancer cells.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details unavailable.