Breast cancer and expression of aromatase in breast adipose tissue.
Extraglandular conversion of C19 steroids to estrogens takes place primarily in the stromal cell component of adipose tissue and is catalyzed by an enzyme complex comprising aromatase cytochrome P450 (P450arom; the product of the CYP19 gene) together with the flavoprotein NADPH-cytochrome P450 reductase. It has been proposed that increased local aromatase activity in breast adipose tissue may influence the growth o f breast carcinomas. Using competitive polymerase chain reaction following reverse transcription (RT-PCR), we quantified P450arom transcripts in breast adipose tissue from mastectomy specimens. In 10 of 15 patients, the highest transcript levels were found in the quadrant where the tumor was located. We also found the highest proportions of adipose stromal cells versus adipocytes in these quadrants. These findings suggest that regional differences in the relative proportions o f these histologic components give rise to local elevated concentrations of estrogens. Although the initiating events are not known, once a neoplastic change has occurred, tumor growth may be promoted by these locally increased estrogen levels. Our data regarding hormonally regulated use of tissue-specific promoters for CYP19 gene transcription suggest preferential utilization of certain upstream regulatory regions of the gene in breast adipose tissue, resulting in increased expression of aromatase.
Bulun
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Cecil H. and Ida Green Center for Reproductive Biology Sciences, Departments of Obstetrics-Gynecology and Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75235-9051, USA.
Simpson
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