Pancreatic cancer accounts for more than 30,000 deaths per year, making it the fourth leading cause of cancer death in the United States. A better understanding of the genetic and molecular basis of pancreatic cancer is needed in order to develop novel and effective diagnostic and therapeutic targets against this disease. Previously, we used array-based Comparative Genomic Hybridization (aCGH) to identify novel regions of DNA amplification in a panel of pancreatic cancer cell lines. The current study is focused on SMURF1, a candidate oncogene found within a highly-localized amplicon at chromosomal region 7q21. SMURF1 is an E3 ubiqutin ligase which has been characterized to inhibit TGF-beta signaling and to promote cell motility, but its role in pancreatic carcinogenesis remains unexplored. We now show that pancreatic cancer cell lines with SMURF1 amplification exhibit elevated SMURF1 mRNA and protein levels. By fluorescence in situ hybridization (FISH) and immunohistochemistry on paraffin sections, we also find that SMURF1 is amplified and/or overexpressed in a subset of primary pancreatic adenocarcimomas. Finally, overexpression of SMURF1 in NIH-3T3 fibroblasts leads to cell transformation (increased focus formation). Our findings support a novel role of SMURF1 amplification in the pathogenesis of pancreatic cancer.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA