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 the 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 compared with normal breast tissue. Other studies suggest that such alterations in the ratio of immunophilins might potentially influence steroid receptor 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 expression was increased approximately five- and 14-fold, respectively. The corresponding protein levels were also elevated in comparison to controls. The antiestrogen, ICI 182,780, was an antagonist for CyP40 and FKBP52 mRNA induction. Cycloheximide treatment did not inhibit this increased immunophilin expression, suggesting that estradiol-mediated activation is independent of de 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 actinomycin D studies. These results suggest that estradiol regulates CyP40 and FKBP52 mRNA expression through both transcriptional and posttranscriptional mechanisms.
Kumar
P
P
Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, WA 6009, Australia.
Mark
P J
PJ
Ward
B K
BK
Minchin
R F
RF
Ratajczak
T
T
D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D000081406:Peptidyl-Prolyl Isomerase F; D004965:Estrogen Antagonists; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D000077267:Fulvestrant; D004958:Estradiol; D003513:Cycloheximide; D021983:Cyclophilins; D022021:Tacrolimus Binding Proteins; C403485:tacrolimus binding protein 4; D019696:Peptidylprolyl Isomerase