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PRKC-ζ expression promotes the aggressive phenotype of human prostate cancer cells and is a novel target for therapeutic intervention

Yao, Sheng; Bee, Alix; Brewer, Daniel; Dodson, Andrew; Beesley, Carol; Ke, Youqiang; Ambroisine, Laurence; Fisher, Gabrielle; Moller, Heinrich; Dickinson, Tim; Gerard, Patricia; Lian, Lu-Yu; Risk, Janet; Lane, Brian; Smith, Paul; Reuter, Victor; Berney, Daniel; Gosden, Christine; Scardino, Peter; Cuzick, Jack; Djamgoz, Mustafa B.A.; Cooper, Colin and Foster, Christopher S. (2010) PRKC-ζ expression promotes the aggressive phenotype of human prostate cancer cells and is a novel target for therapeutic intervention. Genes & Cancer, 1 (5). pp. 444-464. ISSN 1947-6027 (Online); 1947-6019 (Print)

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Abstract

We show Protein Kinase C-zeta variant “b” (PKC-ζ-b) to be a novel predictive biomarker for survival from prostate cancer (p < 0.001). We also confirm that transcription of the PRKC-ζ gene is crucial to the malignant phenotype of human prostate cancer. Following siRNA silencing of PRKC-ζ in PC3-M prostate cancer cells, stable transfectant cell-line si-PRKC-ζ-b-PC3-MT1-6 is phenotypically non-malignant in-vitro and in-vivo. Genome-wide expression analysis identified 373 genes to be differentially expressed in the knockdown cells and four key gene-networks to be significantly perturbed during phenotype modulation. Functional interconnection between some of the modulated genes is revealed, although these may be within different regulatory pathways, emphasizing the complexity of their mutual interdependence. Genes with altered expression following PRKC-ζ knockdown include HSPB1, RAD51 and ID1 that we have previously described to be critically important in prostatic malignancy. Since expression of PRKC-ζ-b is functionally involved in promoting the malignant phenotype, we propose PKC-ζ-b as a novel and biologically-relevant target for therapeutic intervention in prostate cancer.

Item Type:Article
Additional Information:Published online 17 June 2010. Issue: May 2010. Available in PubMed Central. Additional author, Paul Smith, included on published version.
Uncontrolled Keywords:Prostate cancer; PRKC-ζ; siRNA
Subjects:R Medicine > RK Dentistry
Departments, Research Centres and Related Units:Academic Faculties, Institutes and Research Centres > Faculty of Medicine > School of Dental Sciences
DOI:10.1177/1947601910376079
Publisher's Statement:© The Author(s) 2010. Yao, Sheng, Bee, Alix, Brewer, Daniel, Dodson, Andrew, Beesley, Carol; Ke, Youqiang; Ambroisine, Laurence, Fisher, Gabrielle, Møller, Heinrich; Dickinson, Tim, Gerard, Patricia, Lian, Lu-Yu, Risk, Janet, Lane, Brian, Smith, Paul, Reuter, Victor, Berney, Daniel, Gosden, Christine, Scardino, Peter, Cuzick, Jack, Djamgoz, Mustafa B. A., Cooper, Colin and Foster, Christopher S. PRKC-ζ Expression Promotes the Aggressive Phenotype of Human Prostate Cancer Cells and Is a Novel Target for Therapeutic Intervention Genes & Cancer May 2010 1: 444-464, first published 17 June 2010 http://dx.doi.org/10.1177/1947601910376079
Refereed:Yes
Status:Published
ID Code:1357
Deposited On:02 Sep 2010 10:23
Last Modified:12 Feb 2013 16:37

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