Background: We previously reported that resveratrol decreased DNA methyltransferase (DNMT) 1 and 3b expression in vitro and demethylates tumor suppressor RASSF-1a in women at increased breast cancer risk. Herein we document the effects of resveratrol on DNMT and miRNA expression in normal and malignant mammary tissue in a rodent model of estrogen dependent mammary carcinoma.
Methods: 89 female rats received slow release 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 weeks of treatment, animals were sacrificed and mammary glands harvested. Matched tumor and normal tissues were available from 36 rats.
Results: DMNT3b (but not DNMT1) differed in tumor vs. normal tissue after lo (p=.04) and hi p=.007) resveratrol. With hi resveratrol, DNMT3b decreased in tumor but increased normal tissue. Hi resveratrol increased miR21, -129, -204 and -489 from 2.5 to >5 fold 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.
Conclusion: Treatment with resveratrol differentially influences malignant vs. normal tissue DNMT3b and miRNA expression. This mechanism of action of resveratrol to influence mammary carcinogenesis warrants further investigation.
Citation Format: Wenyi Qin, Ke Zhang, Kaitlin Clarke, Timothy Weiland, Edward R. Sauter. Epigenetic effects of resveratrol on mammary carcinoma. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr B26.