JWA—A Novel Environmental-Responsive Gene, Involved in Estrogen Receptor-Associated Signal Pathway in MCF-7 and MDA-MB-231 Breast Carcinoma Cells

Abstract

The pyrethroid insecticide fenvalerate and the organophosphorus insecticide phoxim are now the most widely used agents for indoor pest control in China. Fenvalerate was shown to mimic estrogenic activity, whereas phoxim did not induce similar effects. Our previous studies demonstrated that JWA, a novel retinoic acid-inducible and cytoskeleton-associated gene, is also a potential environmental-responsive gene with increased expression to oxidative and heat-shock stresses. In the present study, the influence of both fenvalerate and phoxim was examined on the expression of JWA in MCF-7 (ER+) and MDA-MB-231 (ER−) human breast carcinoma cell lines. Concentrations of 0.01, 1, and 100 μmol/L of fenvalerate or phoxim were selected to treat both MCF-7 and MDA-MB-231 cells at 1, 3, and 5 d, respectively. The MTT results only showed that fenvalerate stimulated MCF-7 cell proliferation. Western blot assay was employed to detect the expressions of JWA and heat-shock proteins (hsp27 and hasp70). The results showed that after treatment with fenvalerate, both JWA and hsp70 showed similar expression patterns in the both cell lines; however, all the expression patterns of JWA, hsp27, and hsp70 were evidently reversed between ER+ and ER− cells. In addition, phoxim-treated cells showed a concentration-dependent relationship in JWA expression at all time points. These results suggest that JWA has similar functions with respect to hsp27 and hsp70, and might be a novel signal molecule in estrogen receptor-related signal transduction pathways in mammalian cells.This work was partially supported by the following grants: National Natural Science Foundation of China (30170812), the Foundation of High-tech Key Project, Education Department, Jiangsu Province (JH01-049), the National Key Basic Research and Development Project (973) (grant 2002CB512900), and the Project of the Ministry of Science and Technology of China (grants 2001-50 and 2000-026).