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 cell growth. In cells cotreated with insulin plus TCDD or TCDF, insulin-induced cell proliferation and [3H]thymidine incorporation were inhibited. In contrast, alpha-naphthoflavone, a partial aryl hydrocarbon (Ah) receptor 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 Kd and Bmax values for binding of [125I]insulin to the insulin receptor (IR); however, in MCF-7 cells cotreated with insulin plus TCDD, the insulin-induced Kd value for IR-ligand binding was decreased and the Bmax value was increased. TCDD induced IR mRNA levels and inhibited several other insulin-induced responses including c-fos protooncogene expression, phosphorylation of the insulin receptor, and a 185-kDa protein in MCF-7 cells.
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Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843-4466, USA.
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D001483:Base Sequence; D001572:Benzofurans / Q000633:toxicity; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007329:Insulin Antagonists / Q000633:toxicity*; D008969:Molecular Sequence Data; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D001572:Benzofurans; D007329:Insulin Antagonists; D000072317:Polychlorinated Dibenzodioxins; C014211:2,3,7,8-tetrachlorodibenzofuran