QUT ePrints

A novel transcript from the KLKP1 gene is androgen regulated, down-regulated during prostate cancer progression and encodes the first non-serine protease identified from the human kallikrein gene locus

Kaushal, Aneel, Myers, Stephen A., Dong, Ying, Lai, John, Tan, Olivia L., Bui, Loan T., Hunt, Melanie L., Digby, Matthew R., Samaratunga, Hemamali , Gardiner, Robert A. , Clements, Judith A., & Hooper, John D. (2008) A novel transcript from the KLKP1 gene is androgen regulated, down-regulated during prostate cancer progression and encodes the first non-serine protease identified from the human kallikrein gene locus. The Prostate, 68(4), pp. 381-399.

View at publisher

Abstract

BACKGROUND: The kallikrein-related (KLK) serine protease, prostate specific antigen is the current marker for prostate cancer (PCa). Other members of the KLK family are also emerging as potential adjunct biomarkers for this disease. Our aim was to identify and characterize novel KLK-related genes with potential as PCa bio-markers. METHODS: Low stringency DNA screening was coupled with amplification techniques to identify novel sequences. Transcripts were examined by Northern blot, RT-PCR, and in situ hybridization analysis and in silico bioinformatics approaches. Protein characterization was performed by Western blot and confocal microscopy analysis. Gene regulation studies were performed by quantitative PCR and promoter reporter assays. RESULTS: We identified a novel kallikrein-related mRNA designated KRIP1 (kallikrein-related, expressed in prostate 1) which, together with the recently reported PsiKLK1 and KLK31P transcripts, is transcribed from KLKP1; a gene evolved from, and located within, the KLK locus. Significantly, in contrast to these other non-coding KLKP1 transcripts, the KRIP1 mRNA generates an approximately 18 kDa intracellular protein-the first non-serine protease identified from the KLK locus. KRIP1 mRNA is abundant only in normal prostate and is restricted to cells of epithelial origin in normal and diseased glands. Ligand binding of the androgen receptor increases transcription from the KLKP1 gene. Consistently, KRIP1 mRNA levels are lower in PCa samples compared to benign prostatic hyperplasia. CONCLUSIONS: Transcription from KLKP1 is reduced as cells de-differentiate on the pathway to malignancy. KLKP1/KRIP1 has potential as a marker of both PCa progression and recent evolutionary events within the KLK locus.

Impact and interest:

10 citations in Scopus
Search Google Scholar™
8 citations in Web of Science®

Citation countsare sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

ID Code: 13691
Item Type: Journal Article
Additional Information: For more information, please refer to the journal's website (see hypertext link) or contact the author.
Keywords: prostate, androgen, kallikrein, KLKP1, prostate cancer, cells and tissue, ihbi, hormone dependent cancer, clements, hooper, kaushal, dong, lai, tan, bui, hunt
DOI: 10.1002/pros.20685
ISSN: 0270-4137
Divisions: Past > QUT Faculties & Divisions > Faculty of Science and Technology
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2008 John Wiley & Sons
Deposited On: 10 Jun 2008
Last Modified: 29 Feb 2012 23:51

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page