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

Lose, Felicity, Lawrence, Mitchell G., Srinivasan, Srilakshmi, O'Mara, Tracy, Marquart, Louise, Chambers, Suzanne, Gardiner, Robert A., Aitken, Joanne F., Spurdle, Amanda B., Batra, Jyotsna, Clements, Judith A. and Australian Prostate Canc BioResour (2012) The kallikrein 14 gene is down-regulated by androgen receptor signalling and harbours genetic variation that is associated with prostate tumour aggressiveness. Biological Chemistry, 393 5: 403-412. doi:10.1515/hsz-2011-0268

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Author Lose, Felicity
Lawrence, Mitchell G.
Srinivasan, Srilakshmi
O'Mara, Tracy
Marquart, Louise
Chambers, Suzanne
Gardiner, Robert A.
Aitken, Joanne F.
Spurdle, Amanda B.
Batra, Jyotsna
Clements, Judith A.
Australian Prostate Canc BioResour
Title The kallikrein 14 gene is down-regulated by androgen receptor signalling and harbours genetic variation that is associated with prostate tumour aggressiveness
Journal name Biological Chemistry   Check publisher's open access policy
ISSN 1431-6730
1437-4315
Publication date 2012-05-01
Sub-type Article (original research)
DOI 10.1515/hsz-2011-0268
Open Access Status File (Publisher version)
Volume 393
Issue 5
Start page 403
End page 412
Total pages 10
Place of publication Berlin, Germany
Publisher Walter de Gruyter GmbH
Language eng
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.
Keyword Androgen regulation
Gleason score
Kallikreins
Klk14
Prostate cancer
Single nucleotide polymorphisms (SNPs)
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published Online: 19 June 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2013 Collection
School of Medicine Publications
 
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