Androgens up-regulate the human prostate-specific antigen messenger ribonucleic acid (mRNA), but down-regulate the prostatic acid phosphatase mRNA in the LNCaP cell line.
To better understand androgen-regulated gene expression in the prostate, we have used Northern blot analysis to study the effects of androgens and other steroid hormones on the steady state levels of several human prostatic mRNAs in the LNCaP cell line. Dihydrotestosterone (40 nM) as well as a synthetic androgen, R1881 (0.1 nM), increased the amounts of prostate-specific antigen (PSA) and human glandular kallikrein mRNAs; at the same time, the level of prostatic acid phosphatase (PAP) mRNA was down-regulated. Incubation of LNCaP cells with medium containing 0.1 or 1 microM R1881 for 3, 7, or 13 days resulted in up-regulation of PSA and human glandular kallikrein mRNAs and down-regulation of PAP mRNA. Thus, the two clinically important prostate-specific marker proteins are inversely regulated in this cell line. The level of human androgen receptor mRNA was also repressed by the androgen treatments. 17 beta-Estradiol and progesterone had effects similar to those of R1881 on gene expression in LNCaP cells. Our results show that the decrease in the amount of secreted PAP and the increase in the amount of secreted PSA caused by androgens and other steroid hormones in the LNCaP cells of epithelial origin are mediated by changes in the levels of the corresponding mRNAs.
Biocenter, University of Oulu, Finland.
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D000135:Acid Phosphatase / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000235:genetics / Q000378:metabolism; D000728:Androgens / Q000494:pharmacology*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D013196:Dihydrotestosterone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism; D008297:Male; D015741:Metribolone / Q000494:pharmacology; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D011374:Progesterone / Q000494:pharmacology; D017430:Prostate-Specific Antigen; D011471:Prostatic Neoplasms; D012333:RNA, Messenger / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D020840:Tissue Kallikreins
D000199:Actins; D000728:Androgens; D000951:Antigens, Neoplasm; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D013196:Dihydrotestosterone; D015741:Metribolone; D011374:Progesterone; D004958:Estradiol; D000135:Acid Phosphatase; D007610:Kallikreins; D020840:Tissue Kallikreins; D017430:Prostate-Specific Antigen