EFFECTS OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) ON INSULIN-INDUCED RESPONSES IN MCF-7 HUMAN BREAST-CANCER CELLS

Insulin stimulated proliferation of MCF-7 human breast cancer cells in serum-free medium, whereas 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 2,3,7,8-tetrachlorodibenzofuran (TCDF) did not affect fell growth . In cells cotreated with insulin plus TCDD or TCDF, insulin-induced c ell proliferation and [H-3]thymidine incorporation were inhibited, In contrast, alpha-naphthaflavone, a partial aryl hydrocarbon (Ah) recept or antagonist, blocked the inhibitory effects of TCDD, suggesting that the Ah receptor was involved in TCDD-induced responses in MCF-7 cells . TCDD alone did not affect K-d and B-max values for binding of [I-125 ]insulin to the insulin receptor (IR); however, in MCF-7 cells cotreat ed with insulin plus TCDD, the insulin-induced K-d value for IR-ligand binding was decreased and the B-max value was increased, TCDD induced IR mRNA levels and inhibited several other insulin-induced responses including c-fos protooncogene expression, phosphorylation of the insul in receptor, and a 185-kDa protein in MCF-7 cells. (C) 1996 Academic P ress, inc.