Androgen regulation of the messenger RNA encoding diazepam-binding inhibitor/acyl-CoA-binding protein in the human prostatic adenocarcinoma cell line LNCaP.
To study the mechanisms by which androgens intervene in the regulation of growth and differentiation of human prostatic epithelial cells, cDNA clones encoding putative prostate-secreted proteins were characterized and tested as potential markers for androgen action. One of the isolated cDNAs expressed diazepam-binding inhibitor/acyl-CoA-binding protein (DBI/ACBP), suggesting that this polypeptide, that has been implicated in a large number of biochemical processes, is expressed and secreted by prostate cells. As demonstrated by Northern blot analysis, the mRNA encoding DBI/ACBP was expressed in prostate tissue and in the three human prostatic adenocarcinoma cell lines tested: LNCaP, PC-3 and DU-145. In androgen-sensitive LNCaP cells, the synthetic androgen R1881 stimulated the DBI/ACBP steady state mRNA levels with half maximal effects at a concentration of 0.2 nM. Increases were a maximal 12 h after addition of the synthetic hormone. DBI/ACBP mRNA levels could also be stimulated by the synthetic androgen mibolerone and by the natural androgens testosterone and dihydrotestosterone. In agreement with the altered steroid specificity of the androgen receptor in LNCaP cells, estradiol and progesterone also exerted a stimulatory effect. Cortisol and the synthetic glucocorticoid dexamethasone were without effect. Androgen stimulation of DBI/ACBP mRNA levels was abolished in the presence of the protein synthesis inhibitor cycloheximide, implying a role for labile or androgen-induced proteins in this androgen stimulation. This is in contrast to the androgen stimulation of the mRNA encoding prostate-specific antigen (PSA), suggesting that different mechanisms are involved in the androgen regulation of these two genes. Although further experiments are required to confirm that DBI/ACBP is secreted by prostatic epithelial cells, these data demonstrate that the mRNA encoding DBI/ACBP is expressed in prostate cells and is affected by androgens in androgen-responsive LNCaP cells.
Swinnen
J V
JV
Laboratory for Experimental Medicine and Endocrinology, Faculty of Medicine, Catholic University of Leuven, Belgium.
Esquenet
M
M
Heyns
W
W
Rombauts
W
W
Verhoeven
G
G
D000230:Adenocarcinoma / Q000378:metabolism*; D000728:Androgens / Q000494:pharmacology*; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics*; D003001:Cloning, Molecular; D003513:Cycloheximide / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D026261:Diazepam Binding Inhibitor; D013196:Dihydrotestosterone / Q000494:pharmacology; D006801:Humans; D007106:Immune Sera; D008297:Male; D015741:Metribolone / Q000494:pharmacology; D009277:Nandrolone / Q000031:analogs & derivatives / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000235:genetics; D011471:Prostatic Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D013739:Testosterone / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000728:Androgens; D002352:Carrier Proteins; D018076:DNA, Complementary; D026261:Diazepam Binding Inhibitor; D007106:Immune Sera; D012333:RNA, Messenger; D013196:Dihydrotestosterone; D015741:Metribolone; D013739:Testosterone; D009277:Nandrolone; D003513:Cycloheximide; C100075:mibolerone; D017430:Prostate-Specific Antigen