The class of endocrine disrupting chemicals (EDCs) is comprised of both naturally occurring and man-made compounds which are structurally similar or distinct to estrogen, and can interfere with the actions of an endogenous steroid hormone via estrogen receptors (ERs). Octylphenol (OP) is alkyl phenol chemical, which is considered to be a low-level endocrine disruptor owing to its tendency to mimic estrogen. It has been reported that triclosan can cause endocrine disruption and has weak estrogenic properties with binding to ERs. In this study, we examined that these EDCs, which have an estrogenic activity, can induce cell growth of human breast cancer cells via an ER-dependent signaling pathway by using the cell proliferation assay, semi-quantitative RT-PCR and Western blot analysis. Treatments of MCF-7 breast cancer cells with OP and triclosan resulted in the stimulation of their cell gorwth and induced the alteration of transcriptional and translational levels of cell cycle-related genes. These OP and triclosan increased the proliferation of MCF-7 breast cancer cells in a dose-dependent manner, similar to 17-beta estradiol (E2). We also found that they caused the induction of cyclin D1 gene and reduction of p21 gene at tranlational levels. It can be assummed that the alterations of genes associated with G1/S transition in MCF-7 cells by OP and triclosan may result in the increase of cell growth. However, cell growth and alteration of genes caused by OP and tricalosan can be reversed by an ER antagonist, ICI 182,780, in these cells. An activation of an ERa signaling pathway by propyl pyrazoletriol (PPT) can promote the stimulatory effect of OP and triclosan on the alteration of transcriptional regulation in cell cycle. To ensure the effect of these EDCs on ERa, we knowdowned ERa by siRNA in MCF-7 cells. When ERa level was knockdowned in these cells, the effects of these EDCs on the upregulation of cyclin D1 and downregulation of p21 disappeared. Taken together, OP and triclosan can lead to stimulate breast cancer cell growth via the alterations of cyclin D1 and p21 genes in human breast cancer cells through an ER-mediated signaling pathway. A further study is required to determine the effects of EDCs on breast cancer carcinogenesis in vivo.
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.
05 - 09 May 2012
European Society of Endocrinology