Estradiol-regulated expression of the immunophilins cyclophilin 40 and FKBP52 in MCF-7 breast cancer cells

The immunophilins, cyclophilin 40 (CyP40) and FKBP52, are associated with t he unactivated estrogen receptor in mutually exclusive heterocomplexes and may differentially modulate receptor activity, We have recently shown that CyP40 and FKBP52 mRNA's are differentially elevated in breast carcinomas co mpared with normal breast tissue. Other studies suggest that such alteratio ns ill the ratio of immunophilins might potentially influence steroid recep tor function. Studies were therefore initiated to investigate the influence of estradiol on CyP40 and FKBP52 expression in MCF-7 breast cancer cells. Over a 24-h-treatment period with estradiol, CyP40 and FKBP52 mRNA expressi on was increased approximately five- and 14-fold, respectively. The corresp onding protein levels were also elevated in comparison to controls. The ant iestrogen, ICI 182,780, was an antagonist for CyP40 and FKBP52 mRNA inducti on. Cycloheximide treatment did not inhibit this increased immunophilin exp ression, suggesting that estradiol-mediated activation is independent off d e novo protein synthesis. Treatment of MCF-7 cells with estradiol resulted in an increased half-life of both CyP40 and FKBP52 mRNA, as determined by a ctinomycin D studies. These results suggest that estradiol regulates CyP40 and FKBP52 mRNA expression through both transcriptional and posttranscripti onal mechanisms. (C) 2001 Academic Press.