Abstract |
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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Authors | H Liu, S Safe |
Journal | Toxicology and applied pharmacology
(Toxicol Appl Pharmacol)
Vol. 138
Issue 2
Pg. 242-50
(Jun 1996)
ISSN: 0041-008X [Print] United States |
PMID | 8658525
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Benzofurans
- Insulin Antagonists
- Polychlorinated Dibenzodioxins
- 2,3,7,8-tetrachlorodibenzofuran
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Topics |
- Base Sequence
- Benzofurans
(toxicity)
- Breast Neoplasms
(metabolism, pathology)
- Carcinoma
(metabolism, pathology)
- Cell Division
(drug effects)
- Humans
- Insulin Antagonists
(toxicity)
- Molecular Sequence Data
- Polychlorinated Dibenzodioxins
(toxicity)
- Tumor Cells, Cultured
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