Objectives: Establishing more effective treatment of pancreatic cancer requires an understanding of the molecular events leading to the onset and progression of this disease. The biology of tumorigenesis may be better understood if cell type-specific genes in the pancreas are more recognized. This recognition may be as important as discovering a disease-responsible gene. Identification of a ductal epithelium-specific gene can contribute not only to our knowledge of pancreatic tumorigenesis, tumor marker discovery, and effective drug targeting but also is crucial for making a reliable animal model.
Methods: We used the x-Profiler engine online to compare the SAGE (Serial Analysis of Gene Expression) libraries derived from 2 short-term cultures of normal human ductal epithelial cells from the pancreas against 34 other SAGE libraries generated from other normal human tissues to identify the best candidate gene specific for the ductal epithelium of the pancreas.
Results: We identified 3 genes, ribosomal protein L38 (RPL38), uridine phosphorylase (UPP1), and FOS-like antigen-1 (FOSL1), predominantly expressed in the pancreatic ductal epithelium. The expression patterns of these 3 genes were confirmed by virtual Northern analysis, semi-quantitative RT-PCR, and in situ hybridization.
Conclusion: Although the expressions of these 3 genes are not completely restricted to the ductal epithelium of the pancreas, we showed that they have more specific expression patterns than CK19 and MUC1. We also demonstrated that all 3 genes are highly expressed in a panel of pancreatic cancer cell lines and can potentially be useful in tumor targeting or as tumor markers.