The role of aromatase in breast tumors.
Aromatization of androstenedione to estrone in peripheral tissues is the major source of estrogen in postmenopausal women. The aromatase enzyme complex, which mediates the conversion of androstenedione to estrone, is present in several tissues, including adipose tissue and normal and malignant breast tissues. Aromatase activity is detectable in 50-60% of breast tumors, but the contribution that tumor aromatase makes to estrogen concentration in tumors and whether the estrogen formed is biologically important remains a controversial matter. Since concentrations of androstenedione are higher in tumors than in blood, and tumor aromatase activity in vivo may be enhanced by growth factors and by cytokines, the contribution of tumor aromatase to tumor estrogen levels may be higher than suggested by the original calculations. Measurements of tumor aromatase, tumor estrone concentrations, and DNA polymerase alpha activity (a marker of cellular proliferation), in samples obtained before and after treatment with the aromatase inhibitor 4-hydroxyandrostenedione, lend some support to a biological role for estrone formed locally.
Reed
M J
MJ
Unit of Metabolic Medicine, St. Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, UK.
D000735:Androstenedione / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000378:metabolism; D004257:DNA Polymerase II / Q000378:metabolism; D004967:Estrogens / Q000096:biosynthesis / Q000378:metabolism*; D004970:Estrone / Q000378:metabolism; D005260:Female; D006801:Humans; D011379:Prognosis; D011980:Receptors, Progesterone / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D004967:Estrogens; D011980:Receptors, Progesterone; D004970:Estrone; D000735:Androstenedione; D001141:Aromatase; D004257:DNA Polymerase II; C014594:formestane