Expression and significance of casein kinase 1 alpha in prostate cancer initiation and progression

Abstract

Prostate cancer (PC) is the first cause of death related to the reproductive system in men. One out of seven men encounters this pathology once in his lifetime. Prostate Specific Antigen along with digital rectal exam are the standard screening techniques for prostate pathologies. Many studies showed that these techniques are not reliable. New biomarkers are therefore needed that help get an early-detection and efficient treatment of PC. Casein Kinase 1 Alpha (CK1α) is an enzyme involved in multiple cellular processes such as the regulation of the oncogenic Wnt/beta-catenin signaling pathway. Although a recent study suggests a correlation of CK1α expression with PC, its implication in carcinogenesis and cancer progression is still unclear. In this study, we aim to establish a CK1α expression profile in benign prostate hyperplasia (BPH) compared to differently advanced PC grades and to investigate a correlation of the enzyme with Wnt-beta catenin pathway in the different samples. We collected formalin-fixed paraffin-embedded human BPH and PC tissues, along with extracts from normal prostatic epithelial cells and PC cell lines. Gene expression was assessed by quantitative RT-PCR. Protein localization was monitored by tissue immunostaining for CK1α and beta-catenin. CK1α protein levels were quantified in cell lines by immunoblotting. We were able to identify a continuous increase in the CK1α transcript expression between controls and PC. Similar mRNA overexpression was detected in cell lines. Preliminary immunostaining results showed membranous beta catenin in all sections. Our results nominate CK1α as a potential biomarker for PC and point to a probable role in the proliferation induction axis, and malignant behavior of cells. Our staining results suggest that there is no correlation between CK1α and the oncogenic Wnt/beta-catenin pathway in PC from which emerges the need to deeply investigate the pathways in which CK1α is implicated in PC initiation and progression.