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Hum Exp Toxicol. 2004 Dec;23(12):555-64.

Disruption of estrogen-regulated gene expression by dioxin: downregulation of a gene associated with the onset of non-insulin-dependent diabetes mellitus (type 2 diabetes).

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Department of Anatomy and Public Health, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA.


Expression of an estrogen-regulated reporter gene, growth of MCF-7 cells in the presence of 17beta-estradiol (E2) or E2 plus TCDD, and DNA microarray plus real time quantitative PCR analyses of gene expression in MCF-7 cells were used to evaluate the effects of TCDD, a known E2 antagonist, on E2-regulated gene expression in human cells. TCDD added simultaneously with E2 exhibited significantly decreased E2-associated upregulation of reporter gene expression compared with cells treated with E2 alone, and decreased E2 enhancement of mitosis in MCF-7 cells. MCF-7 cells treated with E2 or E2 plus TCDD and DNA microarray-evaluated to determine patterns of gene expression, showed substantial differences in gene expression in TCDD-treated cells compared with E2-treated cells. Of the 2400 genes on the Perkin Elmer global array microchip utilized for this analysis, a minimum of 317 were significantly upregulated and 488 were significantly downregulated. Of these, the gene encoding insulin receptor substrate-1 (IRS-1), the protein product of which has been previously reported to be decreased, missing, altered, or defective in persons with type 2 diabetes mellitus, was evaluated by real time quantitative PCR to corroborate the array data. An evaluation of the potential consequences of TCDD-altered IRS-1 downregulation is presented.

[Indexed for MEDLINE]

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