Cancer in Man

Down-Regulation of Estrogen Receptors by Androgens in the ZR-75-1 Human Breast Cancer Cell Line*

“…The lack of fundamental studies illustrating the mechanisms responsible for the potent inhibitory effects of androgens on breast cancer cell growth probably explains the limited use of androgens in the clinical practice of breast cancer endocrine therapy, which is classically limited to antiestrogens. Pituitary suppression of gonadotropin secretion cannot solely explain the clinical efficacy of androgens since their benefits are unrelated to menopausal status (1). Despite the fact that androgens behave as estrogen agonists at supraphysiological concentrations (4)(5)(6)(7)(8)(9)(10)(11), physiological concentrations of androgens (0.01-10 nM) have recently been found to strongly decrease growth rate and cell saturation density through their interaction with the androgen receptor (AR) in the estrogen-responsive ZR-75-1 human breast cancer cell line (12).…”

“…Such data on ER expression provide an explanation for at least part of the antiestrogenic effects of androgens on breast cancer cell growth and moreover suggest that the specific inhibitory effects of androgen therapy could be additive to the standard treatment limited to blockade of estrogens by antiestrogens. (Endocrinology 125: [392][393][394][395][396][397][398][399]1989) F ROM 20-50% of women with advanced breast cancer respond to androgen therapy (1)(2)(3). The lack of fundamental studies illustrating the mechanisms responsible for the potent inhibitory effects of androgens on breast cancer cell growth probably explains the limited use of androgens in the clinical practice of breast cancer endocrine therapy, which is classically limited to antiestrogens.…”