The aromatase enzyme is a cytochrome P-450 complex, widely expressed in different tissues, such as brain, breast, ovary, testes, endometrium skin, bone and fat. In premenopausal women, the ovaries are the main sources of estrogen synthesis, while after menopause aromatase mediates locally the conversion of androstenedione to estrone and testosterone to estradiol at extragonadal sites. In healthy postmenopausal women, serum estrogen levels are strongly decreased, whereas estrogen concentrations in the breast may be much higher, quite similarly to the premenopausal period. Maintenance of the local estrogen concentration in the breast tissue of older women is mistakenly regarded as a possibility for estrogen induced cancer development in spite of the low circulating estrogen levels. Considering that estrogens are crucial players in the safety regulation of cell proliferation, local estrogen synthesis in the breast after cessation of ovarian hormone production has similar compensatory role as that of local generators in case of short circuit. The concept of estrogen induced breast cancer development was erroneously supported by the increased aromatase activity of tumor associated breast quadrants as compared with non involved quadrants. Nevertheless, the measurements of local aromatase activities in correlation with the clinical outcome of disease supported the tumor inhibitory action of local estrogen synthesis. Selective estrogen receptor blockers and aromatase inhibitors were developed for the inhibition of estrogen signaling so as to block estrogen receptor activities and the presumably associated proliferation of breast cancer cells. Transitory anticancer effect of antiestrogens in near 30% of breast cancer cases is a deceiving experience, since tumor regression may be attributed to the alarmed overexpression of estrogen receptors and aromatase enzyme, counteracting the artificial defect of estrogen signaling. Later, the exhaustion of defensive counteractions results in tumor spread, being evaluated as “acquired antiestrogen resistance”.
|Number of pages||17|
|Journal||International Journal of Cancer Research and Prevention|
|Publication status||Published - Jan 1 2015|
ASJC Scopus subject areas
- Social Psychology