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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 30 (1994), S. 19-29 
    ISSN: 1573-7217
    Keywords: adipose tissue ; alternative promoters ; aromatase regulation ; estrogen biosynthesis ; RT-PCR ; stromal cells ; tumor origins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Extraglandular conversion of C19 steroids to estrogens takes place primarily in the stromal cell compartments of adipose tissue and is catalyzed by aromatase cytochrome P450 (P450arom, the product of the CYP19 gene). CYP19 gene expression and aromatase activity in breast adipose stromal cells in culture are subject to complex hormonal regulation, which was recently found to be mediated in part by alternative use of tissue-specific promoters of the CYP19 gene. It has been proposed that increased local aromatase activity in breast adipose tissue may influence the growth of breast carcinomas. Using competitive RT-PCR, we quantified P450arom transcripts in breast adipose tissue from mastectomy specimens. In 10 out 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 vs. adipocytes in these quadrants. These findings suggest that regional differences in the relative proportions of the 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. We are currently investigating alternative promoter use for CYP19 gene transcription to explain this association. Our results underscore the importance of aromatase inhibitors as effective agents in treatment of hormone-responsive breast cancer, since aromatase inhibitors reduce local aromatase activity as well as blood estradiol levels.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of mammary gland biology and neoplasia 5 (2000), S. 251-258 
    ISSN: 1573-7039
    Keywords: aromatase ; breast adipose ; tumor ; cytokines ; prostaglandins ; specific aromatase modulators
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract While the ovaries are the principal source of systemic estrogen in the premenopausal nonpregnant woman, other sites of estrogen biosynthesis are present throughout the body and these become the major sources of estrogen beyond menopause. These sites include the mesenchymal cells of the adipose tissue and skin, osteoblasts, and perhaps chondrocytes in bone, vascular endothelial and aortic smooth muscle cells, as well as a number of sites in the brain including the medial preoptic/anterior hypothalamus, the medial basal hypothalamus and the amygdala. These extragonadal sites of estrogen biosynthesis possess several fundamental features which differ from those of the ovaries. Principally, the estrogen synthesized within these compartments is probably only biologically active at a local tissue level in a paracrine or `intracrine' fashion. Thus the total amount of estrogen synthesized by these extragonadal sites may be small, but the local tissue concentrations achieved are probably quite high, and exert significant biological influence locally. Thus these sources of estrogen play an important but hitherto largely unrecognized, physiological and pathophysiological role.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
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