Kaushal, A and Myers, SA and Dong, Y and Lai, J and Tan, OL and Bui, LT and Hunt, ML and Digby, MR and Samaratunga, H and Gardiner, RA and Clements, JA and Hooper, JD, A Novel Transcript Fromthe KLKP1Gene Is Androgen Regulated,Down-Regulated During Prostate Cancer Progression and Encodes the First Non-Serine Protease Identified Fromthe Human Kallikrein Gene Locus, The Prostate, 68 pp. 381-399. ISSN 0270-4137 (2008) [Refereed Article]
Copyright 2008 Wiley-Liss
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 (kallikreinrelated, expressed in prostate 1) which, together with the recently reported CKLK1 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 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.
|Item Type:||Refereed Article|
|Research Division:||Biological Sciences|
|Research Field:||Genome Structure and Regulation|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Objective Field:||Cancer and Related Disorders|
|Author:||Myers, SA (Dr Stephen Myers)|
|Web of Science® Times Cited:||17|
|Deposited By:||Health Sciences B|
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