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In these patients, biologically active estrogens are locally produced from circulating inactive steroids including adrenal androgens in an intracrine mechanism in the breast cancer tissues and confer estrogenic activities on carcinoma cells. A series of enzymes are involved in this intra\u2010tumoral or <jats:italic>in situ<\/jats:italic> production of estrogens in breast carcinoma tissues but aromatase, a member of the cytochrome P450 family, is a key enzyme of estrogen production through conversion from circulating adrenal androgens in estrogen\u2010dependent postmenopausal breast cancer. It then becomes important to identify the sites of this estrogen production. There has been, however, controversy regarding intra\u2010tumoral localization of aromatase in breast carcinoma, especially whether intra\u2010tumoral production of estrogens through aromatase occurs in carcinoma or stromal cells. The enzyme was demonstrated to be expressed in both carcinoma and stromal cells in breast carcinoma tissues on immunohistochemistry with a well\u2010characterized mAb 677 and combined laser capture microdissection\/qualitative reverse transcriptase\u2013polymerase chain reaction. Intra\u2010tumoral aromatase in both of these cell types was subsequently demonstrated to be induced by carcinoma\u2013stromal interactions associated with carcinoma invasion in breast tissue. The signals through various nuclear receptors, especially estrogen\u2010related receptor\u2010\u03b1 in carcinoma cells and liver receptor homologue\u20101 in adipocytes adjacent to carcinoma invasion, in conjunction with various cytokines and\/or growth factors, play pivotal roles in this induction of intra\u2010tumoral aromatase. This increased aromatase subsequently results in increased <jats:italic>in situ<\/jats:italic> estrogen concentrations of breast cancer. Aromatase inhibitors are currently established as the gold standard for the treatment for ER\u2010positive breast carcinoma but resistance to the therapy still remains to be solved by other modes of suppression of intra\u2010tumoral estrogen production.<\/jats:p>","DOI":"10.1111\/j.1440-1827.2009.02444.x","type":"journal-article","created":{"date-parts":[[2009,10,27]],"date-time":"2009-10-27T04:31:07Z","timestamp":1256617867000},"page":"777-789","source":"Crossref","is-referenced-by-count":72,"title":["<i>In situ<\/i> estrogen production and its regulation in human breast carcinoma: From endocrinology to 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