Abstract 1612: Validation of CSE1L/hCAS as a potential therapeutic target in pancreatic cancer

Abstract

Abstract Background: The nuclear export protein CSE1L/hCAS has recently gained attention as a putative oncogene, which is amplified in several human malignancies. The role of hCAS in pancreatic cancer is unknown. In this work, we sought to evaluate the expression of hCAS in pancreatic cancer cell lines and tumor tissue and to further explore the potential of hCAS as a therapeutic target. Methods: The nuclear and cytosolic hCAS protein expression was determined in human pancreatic cancer cell lines and tumor tissues and compared with those of immortalized normal pancreatic ductal cells and normal pancreatic tissues. The cellular effects of hCAS knockdown using small interfering RNA oligonucleotides were investigated in MiaPaCa-2 human pancreatic cancer cells with regard to proliferation (MTT assay), cell death (Trypan blue and Flow cytometry), and malignant transformation (colony formation assay). Results: hCAS protein expression increased in pancreatic cancer cell lines relative to the immortalized pancreatic ductal epithelial cell line. Immunohistochemical staining of a human pancreatic tumor tissue microarray showed that hCAS expression was higher in pancreatic tumors compared with their normal counterparts. There was increasing nuclear to cytoplasmic staining with progression from normal pancreatic duct to increasing grade of pancreatic intraductal neoplasia to invasive pancreatic cancer. Treatment with hCAS targeting small interfering RNAs effectively reduced pancreatic cell growth in tissue culture, induced apoptosis, and inhibited growth in soft agar. Conclusion: This is the first report of hCAS expression and cellular distribution in human pancreatic cancer. Our data suggest that hCAS might be an attractive target for human pancreatic cancer prevention and therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1612.