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• W2146233029 startingPage "515" @default.
• W2146233029 abstract "Postmenopausal women on estrogen replacement therapy (ERT) have a reduced risk of developing colon cancer compared with postmenopausal women not on ERT, suggesting a role for estradiol (E 2 ) in protection against this disease. To determine whether E 2 protects against inflammation-associated colon cancer when administered following the initiation of colonic DNA damage, in this study, we implanted E 2 -containing pellets into mice after co-treatment with azoxymethane and two rounds of dextran sulfate sodium (DSS). Wild-type (WT) E 2 -treated mice had reduced numbers and average area of adenocarcinomas compared with the control mice. These effects were lost in estrogen receptor-β ( Er β ( Esr2 )) knockout mice. Surprisingly, apoptosis was reduced and cell proliferation was increased in sections from tumors of the WT E 2 mice compared with the WT control mice. These findings are probably due, in part, to a reduction in ERβ expression in colonic epithelial cells as the cells progressed from a non-malignant to a cancerous state as enhanced apoptosis was observed in normal colonocytes expressing higher levels of ERβ. Furthermore, epithelial cells within the tumors had dramatically increased ERα mRNA and protein expression compared with the non-diseased mice. We conclude that while E 2 treatment resulted in an overall suppression of colonic adenocarcinoma formation, reduced ERβ expression accompanied by enhanced ERα expression caused an altered colonocyte response to E 2 treatment compared with the earlier stages of colon cancer development. These data are the first examples of decreased ERβ expression concurrent with increased ERα expression as a disease develops and highlight the importance of understanding the timing of E 2 exposure with regard to the prevention of inflammation-associated colon cancer." @default.
• W2146233029 created "2016-06-24" @default.
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• W2146233029 date "2013-05-23" @default.
• W2146233029 modified "2023-10-18" @default.
• W2146233029 title "A novel shift in estrogen receptor expression occurs as estradiol suppresses inflammation-associated colon tumor formation" @default.
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• W2146233029 doi "https://doi.org/10.1530/erc-12-0308" @default.
• W2146233029 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23702470" @default.
• W2146233029 hasPublicationYear "2013" @default.
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