Identification and androgen-regulated expression of two major human glandular kallikrein-1 (hGK-1) mRNA species.

Abstract:

:The screening of an oligo(dT)-primed prostate cDNA library with a human glandular kallikrein-1 (hGK-1) genomic DNA fragment resulted in the isolation of two different hGK-1 cDNAs. A 1.2 kb cDNA (pGK-1) contains an open reading frame of 510 bp, encoding the major part of the previously predicted hGK-1 protein (Schedlich et al. (1987) DNA 6, 429-437). This cDNA contains a 3'-untranslated region of 677 nucleotides and terminates in a poly(A) stretch, preceded by the canonical AATAAA polyadenylation signal. A second cDNA (pGK-10A), with a size of 1.5 kb, contains an open reading frame of 669 nucleotides preceded by 16 nucleotides of the 5'-untranslated region. pGK-10A differs from pGK-1 by the presence of an additional 37 bp fragment, interrupting the protein coding region of hGK-1, which results from the use of an alternative splice donor site of intron IV of the hGK-1 gene. The mature protein (excluding presumed pre- and propeptides) as deduced from the pGK-10A cDNA sequence, has a size of 199 amino acids and differs at the COOH-terminus from the 237 amino acid hGK-1 protein. The alternatively spliced mRNA comprises approximately 20% of the hGK-1 transcripts, as deduced from analysis of mRNA from prostate cells by PCR amplification of specific fragments. The regulation of hGK-1 mRNA expression was studied in different human prostate tumors and cell lines by Northern blotting, using a hGK-1-specific oligonucleotide probe. A high level of hGK-1 expression was found in the androgen-dependent tumors PC 82 and PC EW. hGK-1 mRNA was also present in the androgen-sensitive LNCaP cell line, but undetectable in the androgen-insensitive prostate tumors PC 133, PC 135 and the PC 3 cell line. In LNCaP cells, the expression of hGK-1 mRNA was strongly induced by androgens. Regulation of expression of the closely related prostate-specific antigen (PA) gene showed a similar pattern.

journal_name

Mol Cell Endocrinol

authors

Riegman PH,Vlietstra RJ,van der Korput HA,Romijn JC,Trapman J

doi

10.1016/0303-7207(91)90272-t

subject

Has Abstract

pub_date

1991-04-01 00:00:00

pages

181-90

issue

1-3

eissn

0303-7207

issn

1872-8057

pii

0303-7207(91)90272-T

journal_volume

76

pub_type

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