Expressionsanalyse von mikrodissiziierten Pankreaskarzinomen und Pankreaskarzinomzelllinien mit DNA-Chips

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains an important cause of malignancy related death. Despite recent progress in understanding the molecular basis of PDAC, further studies are needed to find new molecular markers for diagnostic and therapeutic purposes. We have studied the mRNA-expression profile of microdissected PDAC, of microdissected normal pancreatic duct cells, of one primary normal pancreatic cell line, and of 5 established pancreatic cancer cell lines. We applied DNA microarray technology with a custom made Affymetrix Chip containing 6117 probesets representing 3300 genes among them 1000 known tumor-associated genes. Hierarchical clustering revealed 92 differentially expressed genes in 4 main clusters (upregulated in normal ductal cells: 30 genes; upregulated in normal and cancerous pancreatic tissue versus cell lines: 23 genes; upregulated in PDAC and tumor cell lines versus normal ductal cells: 19 genes; upregulated in cell lines versus primary tissue: 20 genes). Within the 92 genes, 16 were found to represent human genes known to be implicated in tumorigenesis of PDAC. 30 genes have been known in other tumor entities. The remaining 46 genes may represent a valuable source to identify novel tumor suppressor and oncogenes involved in the carcinogenesis of PDAC.