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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

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    Author(s)
    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
    Griffith University Author(s)
    Chambers, Suzanne K.
    Year published
    2012
    Metadata
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    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 ...
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    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.
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    Journal Title
    Biological Chemistry
    Volume
    393
    Issue
    5
    DOI
    https://doi.org/10.1515/hsz-2011-0268
    Copyright Statement
    © 2012 Walter de Gruyter & Co. KG Publishers. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
    Subject
    Biochemistry and cell biology
    Publication URI
    http://hdl.handle.net/10072/47551
    Collection
    • Journal articles

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