期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 321, 期 2, 页码 123-130出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2010.02.035
关键词
Breast cancer; Epigenetics; Aromatase; Breast adipose fibroblasts; Estrogen biosynthesis
资金
- National Health & Medical Research Council of Australia (CDC) [338518]
- Victorian Breast Cancer Research Consortium Inc.
- U.S. Department of Defense [W81XWH-08-BCRP-POSTDOC]
Cytochrome aromatase p450, encoded by the gene CYP19, catalyzes the synthesis of estrogens from androgens. In post-menopausal women, adipose becomes the major site for estrogen production, where basal CYP19 transcription is driven by distal promoter I 4 In breast adipose fibroblasts (BAFs). CYP19 expression is elevated in the presence of tumour-derived factors through use of promoters 13 and 11 We show for the first time that DNA methylation contributes to CYP19 regulation in BAFs and breast cell lines Promoter I 4 and I 3/II-derived mRNA were not dependent on the CpG methylation status within respective promoters However, inhibition of DNA methylation with 5-aza-2'-deoxycytidine resulted in a significant similar to 40-fold induction in CYP19 mRNA expression in BAFs and breast cell lines These studies uncover a new layer of complexity in the regulation of aromatase where CYP19 appears to be inhibited by DNA methylation and evokes the possibility that disruption to this epigenetic regulation may give rise to an increase in aromatase levels in the breast. Published by Elsevier Ireland Ltd
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