Aldona Jakštaitė, Aurelija Maziukienė, Giedrė Šilkūnienė, Antanas Gulbinas, Žilvinas Dambrauskas
Abstract
Pancreatic ductal adenocarcinoma is extremely aggressivecancer and currently available therapies are only minimallyeffective in treating this disease. Tackling this devastating cancerhas been a major challenge to the scientific and medicalcommunities, in part due to its intense therapeutic resistance.There are numerous aspects of this tumor that contribute to itsaggressive behavior, including a number of mutated tumor supressionand apoptosis pathways, altered cellular metabolism andchanges in the epigenetic regulation. In this study we examinedthe association of this post- transcriptional regulation pathway(CUGBP2 and HuR) and the expression of COX-2 and HO-1,which are known to be associated with inhibition of apoptosis,increased tumor invasiveness and resistance to oxidative stressand/or chemotherapy, and promotion of angiogenesis. Westernblot analysis, immunohiostochemistry and quantitative RT-PCRwere employed to show the expression of mRNA and protein innormal pancreas (from organ donors), cancer tissue (surgical specimens).HuR and CUGBP2 expression was lower both at mRNAand protein levels in pancreatic cancer compared to normal tissue(p<0.05). While cytoprotective molecules COX-2 and HO-1 wereoverexpressed at mRNA and protein levels in pancreatic cancercompared to normal pancreas (p<0.05). The decreased or alteredactivity of CUGBP2 and HuR could be associated with highchemoresistance and early dissemination of pancreatic cancerthrough the HO-1 and COX-2 mediated cytoprotective and carcinogenesispathways. These results mandate further functionalstudies and evaluation of post-transcriptional regulation as a newpotential therapeutic target.
Keyword(s): pancreatic adenocarcinoma, post-transcriptional regulation, HuR, CUGBP2, COX-2, HO-1
DOI: 10.5200/sm-hs.2014.128
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