Effects of TGF-beta and TNF-alpha on the expression of tumour-related CAXII and CAIX in prostate tumour cell line, PC3

Abstract

Cancer is the one the most important health problem of today’sand because of the high death risk and being so widespread, ithas became to public health disease. Cancer is described asuncontrolled cell proliferation and invasion, it effects all the tis-sues and organs of the body. Zinc containing carbonic anhydraseenzymes have important roles in different physiological processesas gas exchange, ion transport and acid-base balance. There are15 enzymatically active CA isoforms in mammalian and the roleof these enzymes is catalysis of the hydration of CO2 moleculeand dehydration of HCO3- ions. CAXII and CAIX are bothtumour related genes that induced at the transcriptional level viathe hypoxia-inducible factor-1 mediated pathway, which is acti-vated in tumor cells by hypoxia or by a mutation in the Hippel-Lindau tumor-suppressor gene. Tumour-associated inflammationand tumourigenesis makes several cytokines attractive targets foradjuvant treatment in cancer such as TNF-a. Cytokines havevery important roles in a whole range of body functions fromgeneral maintenance through regulating inflammatory responses.Up to 20% of all cancers arise in association with chronic inflam-mation and immune cells have a broad impact on tumour initia-tion, growth and progression and many of these effects aremediated by proinflammatory cytokinesIn this study, we aimed to evaluate the effects of TGF-bandTNF-aon the expression of tumor-related CAXII and CAIX atmRNA and protein levels in prostate tumour cell line. Thereforecells were treated with cytokines at different concentrations andthe gene expression profiles of CAIX and CAXII were deter-mined after 24, 48 and 72 hours by real time PCR. Western blotand flow cytometry analysis were used for detection of proteinprofiles of treated cells.