Regulation of GCDFP-15 expression in human mammary cancer cells.
Gross cystic disease fluid protein 15 (GCDFP-15) is a major protein component of benign breast gross cysts. It is also found in approximately 50% of all breast cancer specimens. Androgen receptor (AR) mediated regulation of GCDFP-15 expression was investigated in the AR-positive human mammary cancer cell lines MFM-223 and ZR-75-1. Proliferation of MFM-223 and ZR-75-1 cells is inhibited by androgens. Ten nM 5alpha-dihydrotestosterone stimulated the expression of GCDFP-15 mRNA in MFM-223 (ca. 3-fold) and ZR-75-1 cancer cells (ca. 30-fold) as well as the secretion of GCDFP-15 into the culture medium. Competition experiments with DHT and the antiandrogens hydroxyflutamide and casodex confirmed the involvement of the AR in the regulation of GCDFP-15. Both antiandrogens inhibited GCDFP-15 mRNA expression even in the absence of DHT. AR mRNA was down-regulated in MFM-223 and ZR-75-1 cells (80 and 20% of the control, respectively) during incubation with DHT. Our data demonstrate the effective inhibition of GCDFP-15 expression by pure antiandrogens.
Department of Obstetrics and Gynecology, Philipps-University, D-35037 Marburg, Germany.
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Hackenberg
D000726:Androgen Antagonists / Q000494:pharmacology; D000813:Anilides / Q000494:pharmacology; D001053:Apolipoproteins; D053399:Apolipoproteins D; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D013196:Dihydrotestosterone / Q000494:pharmacology; D005485:Flutamide / Q000031:analogs & derivatives / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins; D006801:Humans; D026901:Membrane Transport Proteins; D009570:Nitriles; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014105:Tosyl Compounds; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
C024328:APOD protein, human; D000726:Androgen Antagonists; D000813:Anilides; D001053:Apolipoproteins; D053399:Apolipoproteins D; D002352:Carrier Proteins; D006023:Glycoproteins; D026901:Membrane Transport Proteins; D009570:Nitriles; C488892:PIP protein, human; D012333:RNA, Messenger; D014105:Tosyl Compounds; D013196:Dihydrotestosterone; C014290:hydroxyflutamide; D005485:Flutamide; C053541:bicalutamide