Abstract 2136: Correlating the expression of protein kinase C isozymes with the transformed phenotype in colorectal cancer

Abstract

Abstract Protein Kinase C (PKC) is a family of serine/threonine kinases that are involved in almost every signal transduction cascade in cells. PKC enzymes are activated by second messangers and respond to specific environmental cues. The development of PKC modulators with anti-cancer therapeutic potential is a major target in cancer. However, this task is made difficult because PKC has an important role to play in normal processes and the PKC family consists of at least 9 different isozymes. Our hypothesis is that PKC expression, activity and localisation are altered as colon epithelial cells switch from normal to the transformed state. We are confident that being able to recognise these changes has the potential to be used as a biomarker and prognostic marker in the early detection of colon cancer. Real Time PCR was utilised to compare the gene expression profile of 9 PKC isozymes in matched normal and cancer tissue samples. We found differential expression of the conventional PKCs, with PRKCB (the gene coding for PKC Beta II) being significantly downregulated in the cancer tissue of over 90% of patients (p<0.01,n = 22). This change was closely linked to the progression of the disease. Using tissue microarrays, we also demonstrated significant alterations in both epithelial and stromal levels of PKC Beta II between the patients normal and diseased tissue. The level of PKC Beta II in the diseased tissue was significantly decreased across patients (p<0.01,n = 164) and we associate the decreased expression with tumour stage. In conclusion we suggest that differential expression of PKC Beta II may be an important mechanism regulating the change to the transformed phenotype in colon cancer. Citation Format: Catríona M. Dowling, James J. Phelan, Mary Clare Cathcart, Brian Mehigan, Paul McCormick, Tara Dalton, John C. Coffey, Jacintha O'Sullivan, Patrick A. Kiely. Correlating the expression of protein kinase C isozymes with the transformed phenotype in colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2136. doi:10.1158/1538-7445.AM2015-2136