Tissue-specific and hormonal regulation of human prostate-specific glandular kallikrein.
Kallikreins are involved in the posttranslational processing of a number of specific polypeptide precursors. Previously, human glandular kallikrein (hGK-1) mRNA has been identified in the prostate; however, the hGK-1 protein has not been identified and characterized. Therefore, its physiologic function in the prostate is not known. In this study, we have isolated a full-length hGK-1 cDNA from a human adenocarcinoma cell line, LNCaP. In vitro translation experiments demonstrated that the molecular size of the hGK-1 protein generated from this cDNA is similar to that of prostate-specific antigen (PSA), a protein which is produced exclusively in the prostate. In situ hybridization with a hGK-1-specific oligonucleotide probe (77 bases), which can differentiate hGK-1 mRNA from PSA mRNA, demonstrated the hGK-1 mRNA to be located in the prostate epithelium. The hGK-1 mRNA was colocalized with PSA mRNA in prostatic epithelia. Moreover, in situ hybridization studies revealed that the level of hGK-1 mRNA in human benign prostatic hyperplasia tissues is approximately half that of PSA mRNA. Furthermore, we have demonstrated that hGK-1 mRNA is under androgenic regulation in LNCaP cells. Time course analysis revealed that hGK-1 mRNA levels increased significantly at 5 h of mibolerone treatment and reached maximal levels by 9 h. In addition, hGK-1 mRNA levels were increased by dihydrotestosterone, but not by dexamethasone or diethylstilbestrol treatments. Flutamide, a nonmetabolized anti-androgen, repressed the androgenic effects. These studies suggest that expression of hGK-1 mRNA is regulated by androgen via the androgen receptor.
Young
C Y
CY
Department of Urology, Mayo Clinic/Foundation, Rochester, Minnesota 55905.
Andrews
P E
PE
Montgomery
B T
BT
Tindall
D J
DJ
D000230:Adenocarcinoma; D000951:Antigens, Neoplasm / Q000032:analysis / Q000235:genetics; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D013196:Dihydrotestosterone / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007610:Kallikreins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D009838:Oligodeoxyribonucleotides; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D011467:Prostate / Q000201:enzymology*; D017430:Prostate-Specific Antigen; D011471:Prostatic Neoplasms; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D015183:Restriction Mapping; D020840:Tissue Kallikreins
D000951:Antigens, Neoplasm; D009838:Oligodeoxyribonucleotides; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D013196:Dihydrotestosterone; D007610:Kallikreins; D020840:Tissue Kallikreins; D017430:Prostate-Specific Antigen