Differential effects of aroclors and DDT on growth factor gene expression and receptor tyrosine kinase activity in human breast epithelial cells.

Abstract

Breast cancer is a proliferative disease of mammary cells. Growth factors and growth factor receptors have been shown to play significant roles in breast cancer development and progression. Overexpression of growth factor receptors is commonly detected in primary breast cancers and predicts for a poor clinical prognosis. Environmental polychlorinated hydrocarbons have also been suggested as playing a role in breast cancer development, since polychlorinated biphenyls and DDT have been detected in the breast fat of women with malignant tumors and some of these agents possess estrogenic properties. We have examined the effects of these chemicals on growth factor receptor expression and receptor tyrosine kinase activity in the MCFlOAneoT human breast epithelial cell lines. The results of this research show that aroclor 1221 and 1254, while failing to affect the expression of c-erbB2 or c-Met growth factor receptors, stimulated the receptor tyrosine kinase activity of these receptors. Aroclor 1221 at 0.01 μM and aroclor 1254 at 0.1 μM stimulated c-Met tyrosine phosphorylation by ~7- and 3-fold, respectively, at 24 h post-treatment. p, pβ-DDT, a strongly estrogenic chemical stimulated EGFR receptor tyrosine kinase activity by ~4- and 5-fold at 0.01 and 0.1 μM, respectively. The results obtained from these studies show that these chemicals are capable of stimulating growth factor receptor tyrosine kinase activity and continuing research will provide valuable information on the effects of these chemicals on growth factor receptor-mediated signal transduction processes and the mechanism(s) by which these chemicals may affect cell proliferation and differentiation.