期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 283, 期 1-2, 页码 127-132出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2007.12.003
关键词
aromatase; CYP19; promoter I.3/II; DNA methylation; cAMP response element; epigenesis
资金
- PHS HHS [C67167] Funding Source: Medline
Aromatase expression varies in a tissue-specific manner and among individuals. Aromatase promoter I.3/II, regulated by a cAMP response element (CRE), is normally quiescent in human skin fibroblasts, whereas its hyperactivity may cause local or systemic estrogen excess. We describe the methylation status of 6 CpG dinucleotides within a 571-bp fragment of promoter I.3/II containing a CRE in cAMP-responsive (n = 1) or nonresponsive (n = 3) primary skin fibroblasts cultured from healthy volunteers. Four out of 6 CpG dinucleotides were unmethylated in cAMP-responsive fibroblasts, whereas all 6 CpG dinucleotides were hypermethylated in cAMP-nonresponsive fibroblasts. Basal and cAMP-stimulated aromatase activity and promoter I.3/II activation were significantly higher in the presence of unmethylated DNA. Furthermore, methylation at the CRE interfered with CREB binding. Thus, methylation of CpG dinucleotides within promoter I.3/II regulates aromatase expression and may be one source of inter-individual variability. Furthermore, abnormal methylation of the aromatase promoter may contribute to aromatase overexpression in breast cancer. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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