Down's syndrome-associated Single Minded 2 gene as a pancreatic cancer drug therapy target

We report here a pancreatic cancer drug therapy utility of a gene involved in Down's syndrome. Single Minded 2 gene (SIM2) from Down's Syndrome Critical Region was expressed in pancreatic cancer-derived cell lines as well as in tumor tissues, but not in the normal pancreas. A related member of the SIM family, SIM1, did not show similar specificity. Inhibition by antisense technology of one of the isoforms of SIM2, the short-form (SIM2-s) expression in the CAPAN-1 pancreatic cancer cell line, caused a pronounced growth inhibition and induced cell death through apoptosis. The specificity of antisense was inferred from inhibition of SIM2-s mRNA but not the related members of SIM family. In view of the high mortality rate of pancreatic cancer patients, these findings have important implications for the future of pancreatic cancer treatment. (C) 2003 Elsevier Ireland Ltd. All rights reserved.