RPL38, FOSL1, and UPP1 are predominantly expressed in the pancreatic ductal epithelium.

Pancreatic cancer is associated with poor prognosis and short-term survival and is often diagnosed after the cancer has metastasized. An effective treatment of the advanced disease is still unavailable.1,2 To unravel the molecular basis of this disease and to identify the disease-causing genes, it is essential to define a subset of genes that are specifically expressed in each cell type of the pancreas. This will not only help us to understand the tissue development and disease biology, but it also is useful for targeting and treating the disease. Tissue-specific genes are valuable for making reliable animal models in that successful creation of transgenic or conditional knockout mice largely depends on the tissue specificity of a promoter. Although most human pancreatic neoplasms have a ductal morphology,3 none of the currently available promoter sequence drives expression in a pancreatic ductal epithelium–specific manner. The commonly used promoters favored by the pancreatic cancer research community fall into 3 categories: First, the promoter is pancreas specific but not restricted to the ductal epithelium in the pancreas. The elastase and p48 promoters are prime examples of this first category. Elastase 1 (ELA1) expression is predominantly found in the acinar cells of the pancreas.4 ELA1 promoter induces expression in the acinar and/or islet cells in additional to the ductal epithelium in the pancreas. P48 is part of hetero-oligomeric transcription factor PTF1 that directs the expression of genes in the exocrine pancreas and is required for committing cells to exocrine fate.5 P48 is expressed in the pancreatic primordium in the embryo and is restricted to the exocrine lineage in adult pancreas.6 Second, the promoter is restricted to the ductal epithelium in the pancreas but is not specific to the pancreas. Cytokeratin 19 (CK19) and mucin 1 (MUC1) genes are representatives of this second category. Cytokeratins serve as immunocytochemical markers for epithelial cells,7 and cytokeratins 7, 19, and 20 are expressed in neonatal and adult pancreata. In the pancreas, intense expressions of cytokeratins 19 and 20 are localized to proliferative ductal epithelial and associated islet cells.8 However, CK19 is also expressed in the epithelium of other organs.9,10 Third, the promoters drive expression in both the exocrine and endocrine lineages of the neonatal pancreas but are inactive in exocrine cells of the adult pancreas. For example, Pdx1-expressing cells are detected early during embryogenesis and subsequently give rise to differentiated ductal, islet, and acinar cells.11–13 In adult pancreas, Pdx-1 is mostly in mature β cells and at a lower level in mature acinar cells.14,15 A public database, SAGEmap, was created as a component of the Cancer Genome Anatomy Project (CGAP) to provide a central location for depositing, retrieving, and analyzing human gene expression data.16,17 This database uses serial analysis of gene expression to quantify transcript levels in both malignant and normal human tissues. By accessing SAGEmap (http://www.ncbi.nlm.nih.gov/SAGE), the user can compare transcript populations between any of the posted libraries. In search of a pancreatic ductal epithelium-specific gene or a gene whose promoter is potentially more specific than what the existing promoters such as CK19, MUC1, and ELA1 can offer us, we used the SAGE database to compare a large group of normal tissues with short-term cultures of pancreatic ductal epithelial cultures. Similar use of this database has resulted in the identification of thyroid- and breast-specific genes.18,19