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, Foster Christopher S
Division of Cellular Pathology and Molecular Genetics, University of Liverpool, UK.
Genes Cancer. 2010 May;1(5):444-64. doi: 10.1177/1947601910376079.
We show protein kinase C-zeta (PKC-ζ) 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-PC3-M(T1-6) is phenotypically nonmalignant in vitro and in vivo. Genome-wide expression analysis identified 373 genes to be differentially expressed in the knockdown cells and 4 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 critical in prostatic malignancy. Because expression of PRKC-ζ is functionally involved in promoting the malignant phenotype, we propose PKC-ζ as a novel and biologically relevant target for therapeutic intervention in prostate cancer.
我们发现蛋白激酶C-ζ（PKC-ζ）是一种预测前列腺癌患者生存的新型生物标志物（P < 0.001）。我们还证实PRKC-ζ基因的转录对人类前列腺癌的恶性表型至关重要。在PC3-M前列腺癌细胞中对PRKC-ζ进行siRNA沉默后，稳定转染细胞系si-PRKC-ζ-PC3-M(T1-6)在体外和体内均表现为非恶性表型。全基因组表达分析确定了373个在敲低细胞中差异表达的基因，以及4个在表型调节过程中受到显著干扰的关键基因网络。尽管其中一些调节基因可能处于不同的调控途径，但它们之间的功能联系得以揭示，这强调了它们相互依赖关系的复杂性。PRKC-ζ敲低后表达发生改变的基因包括我们之前描述的在前列腺恶性肿瘤中起关键作用的HSPB1、RAD51和ID1。由于PRKC-ζ的表达在功能上参与促进恶性表型，我们提出PKC-ζ作为前列腺癌治疗干预的一个新型且具有生物学相关性的靶点。
