Journal article
The kallikrein 14 gene is down-regulated by androgen receptor signalling and harbours genetic variation that is associated with prostate tumour aggressiveness
Biological Chemistry, Vol.393(5), pp.403-412
2012
Abstract
Kallikrein 14 (KLK14) has been proposed as a useful prognostic marker in prostate cancer, with expression reported to be associated with tumour characteristics such as higher stage and Gleason score. KLK14 tumour expression has also shown the potential to predict prostate cancer patients at risk of disease recurrence after radical prostatectomy. The KLKs are a remarkably hormone-responsive family of genes, although detailed studies of androgen regulation of KLK14 in prostate cancer have not been undertaken to date. Using in vitro studies, we have demonstrated that unlike many other prostatic KLK genes that are strictly androgen responsive, KLK14 is more broadly expressed and inversely androgen regulated in prostate cancer cells. Given these results and evidence that KLK14 may play a role in prostate cancer prognosis, we also investigated whether common genetic variants in the KLK14 locus are associated with risk and/or aggressiveness of prostate cancer in approximately 1200 prostate cancer cases and 1300 male controls. Of 41 single nucleotide polymorphisms assessed, three were associated with higher Gleason score (≥7): rs17728459 and rs4802765, both located upstream of KLK14, and rs35287116, which encodes a p.Gln33Arg substitution in the KLK14 signal peptide region. Our findings provide further support for KLK14 as a marker of prognosis in prostate cancer. © 2012 by Walter de Gruyter . Berlin . Boston.
Details
- Title
- The kallikrein 14 gene is down-regulated by androgen receptor signalling and harbours genetic variation that is associated with prostate tumour aggressiveness
- Authors
- Felicity Lose (Author) - Queensland University of TechnologyM G Lawrence (Author) - Queensland University of TechnologyS Srinivasan (Author) - Queensland University of TechnologyT O'Mara (Author) - Queensland University of TechnologyL Marquart (Author) - Queensland Institute of Medical ResearchS Chambers (Author) - Griffith UniversityR A Gardiner (Author) - University of QueenslandJ F Aitken (Author) - Griffith UniversityA B Spurdle (Author) - Queensland Institute of Medical ResearchJ Batra (Author) - Queensland University of TechnologyJ A Clements (Author) - Queensland University of Technology
- Publication details
- Biological Chemistry, Vol.393(5), pp.403-412
- Publisher
- Walter de Gruyter GmbH & Co. KG
- Date published
- 2012
- DOI
- 10.1515/hsz-2011-0268
- ISSN
- 1431-6730
- Copyright note
- Copyright © 2012 by Walter de Gruyter. Reproduced here in accordance with the publishers copyright policy.
- Organisation Unit
- University of the Sunshine Coast, Queensland; Office of Research
- Language
- English
- Record Identifier
- 99450320202621
- Output Type
- Journal article
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- Biochemistry & Molecular Biology
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