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The kallikrein 14 gene is down-regulated by androgen receptor signalling and harbours genetic variation that is associated with prostate tumour aggressiveness.
Biol Chem 2012; 393(5):403-12BC

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.

Authors+Show Affiliations

Molecular Cancer Epidemiology Group, Genetics and Population Health Division, Queensland Institute of Medical Research, Herston, Brisbane, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22505522

Citation

Lose, Felicity, et al. "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, no. 5, 2012, pp. 403-12.
Lose F, Lawrence MG, Srinivasan S, et al. The kallikrein 14 gene is down-regulated by androgen receptor signalling and harbours genetic variation that is associated with prostate tumour aggressiveness. Biol Chem. 2012;393(5):403-12.
Lose, F., Lawrence, M. G., Srinivasan, S., O'Mara, T., Marquart, L., Chambers, S., ... Clements, J. A. (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), pp. 403-12. doi:10.1515/hsz-2011-0268.
Lose F, et al. The Kallikrein 14 Gene Is Down-regulated By Androgen Receptor Signalling and Harbours Genetic Variation That Is Associated With Prostate Tumour Aggressiveness. Biol Chem. 2012;393(5):403-12. PubMed PMID: 22505522.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The kallikrein 14 gene is down-regulated by androgen receptor signalling and harbours genetic variation that is associated with prostate tumour aggressiveness. AU - Lose,Felicity, AU - Lawrence,Mitchell G, AU - Srinivasan,Srilakshmi, AU - O'Mara,Tracy, AU - Marquart,Louise, AU - Chambers,Suzanne, AU - Gardiner,Robert A, AU - Aitken,Joanne F, AU - Spurdle,Amanda B, AU - Batra,Jyotsna, AU - Clements,Judith A, AU - ,, PY - 2011/11/18/received PY - 2012/03/13/accepted PY - 2012/4/17/entrez PY - 2012/4/17/pubmed PY - 2012/9/1/medline SP - 403 EP - 12 JF - Biological chemistry JO - Biol. Chem. VL - 393 IS - 5 N2 - 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. SN - 1437-4315 UR - https://www.unboundmedicine.com/medline/citation/22505522/The_kallikrein_14_gene_is_down_regulated_by_androgen_receptor_signalling_and_harbours_genetic_variation_that_is_associated_with_prostate_tumour_aggressiveness_ L2 - https://www.degruyter.com/doi/10.1515/hsz-2011-0268 DB - PRIME DP - Unbound Medicine ER -