The kallikrein 14 gene is down-regulated by androgen receptor signalling and harbours genetic variation that is associated with prostate tumour aggressiveness

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Title The kallikrein 14 gene is down-regulated by androgen receptor signalling and harbours genetic variation that is associated with prostate tumour aggressiveness
Author Lose, Felicity; Lawrence, Mitchell G.; Srinivasan, Srilakshmi; O'Mara, Tracy; Marquart, Louise; Chambers, Suzanne Kathleen; Gardiner, Robert A.; Aitken, Joanne; Spurdle, Amanda B.; Batra, Jyotsna; Clements, Judith A.; BioResource, The Australian Prostate Cancer
Journal Name Biological Chemistry
Year Published 2012
Place of publication Germany
Publisher Walter de Gruyter
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 any 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.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1515/hsz-2011-0268
Volume 393
Issue Number 5
Page from 403
Page to 412
ISSN 1431-6730
Date Accessioned 2012-09-14
Date Available 2013-06-14T04:08:01Z
Language en_US
Research Centre Behavioural Basis of Health; Centre for Health Practice Innovation
Faculty Griffith Health Faculty
Subject Psychology
URI http://hdl.handle.net/10072/47551
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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