Endocrine Abstracts

In the present study, we determined whether two endocrine-disrupting chemicals (EDCs), triclosan (TCS) and octylphenol (OP), are able to alter the expression of two cell cycle regulators, cyclin D1 and p21, in both in vitro and in mouse breast cancer models. In addition, we determined whether the stimulatory effects of OP or TCS on breast cancer progression may be associated with an estrogen receptor (ER)-mediated signaling pathway. Altered expressions of cyclin D1 and p21 were observed in MCF-7 human breast cancer cells treated with TCS and OP. These disruptions were linked to the control of the G1/S transition during carcinogenesis. In a xenograft mouse model, breast tumor masses were established following exposure to TCS and OP for 8 weeks. In these animals, the growth of tumor cells with BrdU-positive nuclei was by treatment with 17β-estradiol (E₂), OP, and TCS compared to a control (corn oil), suggesting that TCS and OP increase DNA synthesis during the S phase in tumor cells. Amplification of cyclin D1 by TCS and OP was also observed in vivo, implying that the effects of these EDCs possessing estrogenic activity alter the expression of genes related to cancer progression. It was of interest that the effects of TCS and OP were reversed by ICI 182 780, an ER antagonist, indicating that EDC-induced activities are mediated by an ER-dependent signaling pathway. Taken together, these results suggest that TCS and OP can adversely affect human health, i.e. by promoting breast cancer progression, via an ER-mediated signaling cascade.