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Splice variant PRKC-ζ(-PrC) is a novel biomarker of human prostate cancer

Lookup NU author(s): Dr Imad Malki

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Abstract

Background: Previously, using gene-knockdown techniques together with genome expression array analysis, we showed the gene protein Kinase C (PKC)-zeta (PRKCZ) to mediate the malignant phenotype of human prostate cancer. However, according to NCBI, the gene has undergone several major iterations. Therefore, to understand the relationship between its structure and biological activities, we have analysed its expressed sequence in prostate cancer cell lines and tissues.Methods: Transcriptome-walking and targeted PCR were used to sequence the mRNA transcribed from PRKCZ. Hydropathy analysis was employed to analyse the hypothetical protein sequence subsequently translated and to identify an appropriate epitope to generate a specific monoclonal antibody.Results: A novel sequence was identified within the 3′-terminal domain of human PRKCZ that, in prostate cancer cell lines and tissues, is expressed during transcription and thereafter translated into protein (designated PKC-ζ_-PrC) independent of conventional PKC-ζ_-a. The monoclonal antibody detected expression of this 96 kD protein only within malignant prostatic epithelium.Interpretation: Transcription and translation of this gene sequence, including previous intronic sequences, generates a novel specific biomarker of human prostate cancer. The presence of catalytic domains characteristic of classic PKC-β and atypical PKC-ι within PKC-ζ_-PrC provides a potential mechanism for this PRKCZ variant to modulate the malignant prostatic phenotype out-with normal cell-regulatory control.

Publication metadata

Author(s): Yao S, Ireland SJ, Bee A, Beesley C, Forootan SS, Dodson A, Dickinson T, Gerard P, Lian LY, Risk JM, Smith P, Malki MI, Ke Y, Cooper CS, Gosden C, Foster CS

Publication type: Article

Publication status: Published

Journal: British Journal of Cancer

Year: 2012

Volume: 107

Issue: 2

Pages: 388-399

Print publication date: 29/05/2012

Date deposited: 23/04/2013

ISSN (print): 0007-0920

ISSN (electronic): 1532-1827

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/bjc.2012.162

DOI: 10.1038/bjc.2012.162

PubMed id: 22644296

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