Expressionsanalyse von Apoptose-assoziierten Genen beim duktalen pankreatischen Adenokarzinom

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the western world. Although some improvements on patients outcome has been observed after complete resection, the impact on long term survival was minimal due to the resistance of pancreatic cancer to apoptotic stimuli. Although there is growing knowledge of the mechanisms of apoptosis, the role of many regulating proteins in pancreatic cancer is still unclear. By means of medline-research we could identify 101 genes, representing the cell death signal-pathway. We analyzed the gene expression of these genes in microdissected pancreatic cancer samples of 19 patients and microdissected normal pancreatic ductal epithelial cell samples of 14 patients using DNA gene expression analysis based on the Affymetrix U133 GeneChip set. Validation of the data was carried out by quantitative RT-PCR. We found 8 genes upregulated and 4 downregulated in PDAC. Several of the upregulated genes like BIRC5/Survivin, DcR3, FAP-1 and the downregulated genes like Bcl-2 and TNF-R1 have been associated with pancreatic cancer before. Nevertheless, of the other differential expressed genes we could validate a dysregulation of Livin/BIRC7 and IL1R2 by means of quantitative RT-PCR which to our knowledge has not been reported previously. These genes might be good candidates for new therapeutic approaches.