Inhibition of insulin-like growth factor-I responses in MCF-7 cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds.
Insulin-like growth factor-I (IGF-I) stimulated the growth and [3H]thymidine uptake in MCF-7 human breast cancer cells grown in serum- and growth factor-inactivated serum-containing media. Cotreatment of the cells with IGF-I plus 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) resulted in a significant decrease in mitogen-induced cell proliferation and [3H]thymidine uptake. Similar effects were observed for cells treated with 2,3,7,8-TCDD and IGF-I plus 17 beta-estradiol. The relative antimitogenic activities of 2,3,7,8-TCDD and related compounds followed the order 2,3,7,8-TCDD greater than 2,3,7,8-tetrachlorodibenzofuran (TCDF) greater than 1,2,7,8-TCDF greater than 1,3,7,8-TCDD which was similar to their aryl hydrocarbon (Ah) receptor binding affinities. The results showed that 2,3,7,8-TCDD did not alter the IGF-I receptor mRNA levels or the KD values for binding of [125I]IGF-I to the IGF-I receptor in MCF-7 cells. However, 2,3,7,8-TCDD significantly decreased the number of IGF-I-induced IGF-I receptor binding sites and this may play a role in the growth-inhibitory properties of 2,3,7,8-TCDD and related compounds and in the 'cross-talk' between the two endocrine-response pathways.
Liu
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Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station 77843-4466.
Biegel
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Narasimhan
T R
TR
Rowlands
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Safe
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S
D001572:Benzofurans / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors*; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives / Q000494:pharmacology*; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000378:metabolism; D014407:Tumor Cells, Cultured
D001572:Benzofurans; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; D004958:Estradiol; C078328:1,2,7,8-tetrachlorodibenzofuran; D007334:Insulin-Like Growth Factor I; C078329:1,3,7,8-tetrachlorodibenzo-4-dioxin; D017526:Receptor, IGF Type 1; C014211:2,3,7,8-tetrachlorodibenzofuran