The control of progesterone receptor expression in MCF-7 breast cancer cells: effects of estradiol and sex hormone-binding globulin (SHBG)

Estradiol controls the gene transcription and expression of many proteins i n breast cancer cells, like the progesterone receptor, PR, that is up-regul ated by the hormone. Moreover: estradiol is one of the crucial factors indu cing the proliferation of breast cancer cells. Sex Hormone-Binding Globulin (SHBG), the plasma carrier for both estradiol and androgens, inhibits the estradiol-induced growth of MCF-7 cells (estrogen-dependent breast cancer c ells), through its membrane receptor (SHBG-R), cAMP and PKA. The anti-estro genic effect of SHBG, which has been described only as far as cell prolifer ation is concerned, could also play a meaningful role in the estradiol cont rol of other factors in breast cancer cells. In the present study, the effe ct of SHBG on the estradiol control of PR expression (both mRNA and protein ) and function (receptor binding capacity) in MCF-7 cells was examined. SHB G inhibited the estradiol-induced up-regulation of PR mRNA as well as prote in level and function. Moreover, the effect of SHBG on estradiol control of PR expression and function was showed to be specific and mediated by PKA. The intermediacy of PKA in the PR expression control, together with the obs ervation that it is effective in the condition in which the SHBG receptor i s activated, supports the hypothesis that the anti-estrogenic effect of SHB G could be receptor-mediated. The ability of SHBG to inhibit estradiol acti on in a specific way in estrogen-dependent breast cancer cells has, therefo re, to be taken into account for the development of future therapeutic stra tegies. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.