Tissue-Specific and Hormonal Regulation of Human Prostate-Specific Glandular Kallikrein

Charles Y.F. Young, Paul E. Andrews, Benjamin T. Montgomery, Donald J. Tindall

Research output: Contribution to journalArticlepeer-review

165 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)818-824
Number of pages7
JournalBiochemistry
Volume31
Issue number3
DOIs
StatePublished - Feb 1 1992

ASJC Scopus subject areas

  • Biochemistry

Fingerprint Dive into the research topics of 'Tissue-Specific and Hormonal Regulation of Human Prostate-Specific Glandular Kallikrein'. Together they form a unique fingerprint.

Cite this