PO-150 Modulation of the expression of casein kinase i isoform alpha in the initiation and progression of prostate cancer

Abstract

IntroductionProstate cancer (PC) is the first cause of fatality related to the reproductive system in men. One out of seven men encounter this pathology once in their lifetime. Prostate Specific Antigen along with digital rectal exam are the first line of screening for prostate pathologies but numerous studies showed that these techniques lack specificity and in sometimes validity for screening. From this notion comes the need to find new biomarkers and molecular players that help get an early detection and effective treatment of PC. Casein Kinase 1 Alpha (CSNK1A1) is an enzyme involved in multiple cellular processes such as the regulation of the oncogenic Wnt/beta-catenin signalling pathway. Its implication in carcinogenesis and cancer progression is still unclear. In this study, we aim to establish a CSNK1A1 expression profile in BPH and in differently advanced PC grades and to investigate the localization of the enzyme compared to beta catenin in the different samples.Material and methodsFormalin-fixed paraffin-embedded human prostatic tissues were collected as follows: 85 BPH, 64 PC and 3 controls. Gene expression was assessed by quantitative RT-PCR of cellular transcripts. Protein localization was monitored by tissue immunostaining for CSNK1A1 and Beta-Catenin. Further in-vitro validation of the results is to be made on normal prostate epithelial cell line and PC cell lines using RT-PCR and western blotting.Results and discussionsWe were able to identify a continuous increase in the CSNK1A1 expression between controls, BPH and PC. These results are being validated in vitro. Preliminary immunostaining results showed membranous beta catenin in BPH and that seemed to be more heterogeneous in PC sections. A correlation with CSNK1A1 localization and amount is still to be achieved. Our results suggest a role of CSNK1A1 in the pathogenesis of BPH and PC by working on the proliferation induction axis, and malignant behaviour of cells. Our staining results suggest a minor role of beta catenin and Wnt pathway in these axes from which emerges the need to deeply investigate the pathways in which CSNK1A1 is implicated in BPH and PC initiation and progression.ConclusionOur results suggest an increase in CSNK1A1 in BPH and PC, which flags this protein as a potential marker in the progression of PC. More investigation is needed to verify whether this protein is involved in cancer initiation or in the direct inhibition of the oncogenic Wnt/beta-catenin signalling pathway and other pathways.