Endogenous aromatization of testosterone results in growth stimulation of the human MCF-7 breast cancer cell line.
Estrogens produced within breast tumors may play a pivotal role in growth stimulation of the breast cancer cells. However, it is elusive whether the epithelial breast cancer cells themselves synthesize estrogens, or whether the surrounding tumor stromal cells synthesize and supply the cancer cells with estrogen. The aromatase enzyme catalyzes the estrogen production, aromatizing circulating androgens into estrogens. The aim of this study was to investigate aromatase expression and function in a model system of human breast cancer, using the estrogen responsive human MCF-7 breast cancer cell line. Cells were cultured in a low estrogen milieu and treated with estrogens, aromatizable androgens or non-aromatizable androgens. Cell proliferation, expression of estrogen-regulated proteins and aromatase activity were investigated. The MCF-7 cell line was observed to express sufficient aromatase enzyme activity in order to aromatize the androgen testosterone, resulting in a significant cell growth stimulation. The testosterone-mediated growth effect was completely inhibited by the aromatase inhibitors letrozole and 4-hydroxy-androstenedione. Expression studies of estrogen-regulated proteins confirmed that testosterone was aromatized to estrogen in the MCF-7 cells. Thus, the results indicate that epithelial breast cancer cells possess the ability to aromatize circulating androgens to estrogens.
Sonne-Hansen
K
K
Department of Tumor Endocrinology, Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark.
Lykkesfeldt
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AE
D000728:Androgens / Q000378:metabolism / Q000494:pharmacology; D000735:Androstenedione / Q000031:analogs & derivatives* / Q000494:pharmacology; D001141:Aromatase / Q000032:analysis / Q000378:metabolism; D047072:Aromatase Inhibitors / Q000494:pharmacology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D004965:Estrogen Antagonists / Q000378:metabolism; D004967:Estrogens / Q000096:biosynthesis / Q000494:pharmacology; D004970:Estrone / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006801:Humans; D000077289:Letrozole; D009570:Nitriles / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism* / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000728:Androgens; D047072:Aromatase Inhibitors; D003470:Culture Media; D004965:Estrogen Antagonists; D004967:Estrogens; D009570:Nitriles; D011960:Receptors, Estrogen; D014230:Triazoles; D004970:Estrone; D013739:Testosterone; D000735:Androstenedione; D000077289:Letrozole; D001141:Aromatase