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  • Title: CpG dinucleotide methylation of the CYP19 I.3/II promoter modulates cAMP-stimulated aromatase activity.
    Author: Demura M, Bulun SE.
    Journal: Mol Cell Endocrinol; 2008 Feb 13; 283(1-2):127-32. PubMed ID: 18201819.
    Abstract:
    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.
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