Methylation and miRNA Effects of Resveratrol on Mammary Tumors vs. Normal Tissue.

Autor: Qin, Wenyi, Zhang, Ke, Clarke, Kaitlin, Weiland, Timothy, Sauter, EdwardR.
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Zdroj: Nutrition & Cancer; Feb2014, Vol. 66 Issue 2, p270-277, 8p
Abstrakt: We reported that resveratrol decreased DNA methyltransferase (DNMT) 1 and 3b expression in vitro and demethylates tumor suppressorRASSF-1ain women at increased breast cancer risk. We investigated the effects of resveratrol on DNMT and miRNA expression in normal and tumor mammary tissue in a rodent model of estrogen dependent mammary carcinoma. Eighty-nine female ACI rats received estradiol plus: low dose (lo) resveratrol, high dose (hi) resveratrol, 5-aza-2-deoxycytidine (Aza), a known inhibitor of DNMTs, or control (no additional treatment). After 21 wk of treatment, animals were sacrificed and mammary glands harvested. Matched tumor/normal tissues were available from 36 rats. DMNT3b (but not DNMT1) differed in tumor vs. normal tissue after lo (P= .04) and hi (P= .007) resveratrol and Aza treatment. With hi resveratrol, DNMT3b decreased in tumor but increased normal tissue. Hi resveratrol increased miR21, −129, −204, and −489 >twofold in tumor and decreased the same miRs in normal tissue 10–50% compared to control. There was an inverse association between DNMT3b and miR129, −204, and −489 in normal and/or tumor tissue. Treatment with resveratrol differentially influences tumor vs. normal tissue DNMT3b and miRNA expression. This mechanism of action of resveratrol to influence mammary carcinogenesis warrants further investigation. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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