Abstract 4011: Evidence supporting a role of c-Myb in pancreatic cancer

Abstract

Abstract The clinical outcome from pancreatic cancer has not improved over the years. This is, in part, due to not well understood disease mechanisms and consequently there is little progress made in developing intervention therapy. Many genetic alterations have been characterized in pancreatic cancer, of which some have been shown to be functionally relevant. In an earlier study, c-Myb was identified as a candidate oncogene in pancreatic cancer with gene amplification in a subset and overexpression in majority of pancreatic cancer tissues and cell lines. The role of c-Myb in pancreatic cancer, however, has not been defined so far. c-Myb is a cellular progenitor of v-Myb oncogenes, which encodes for a transcription factor and confers its oncogenic activity by regulating the expression of several target genes. To examine the functional role of c-Myb in pancreatic cancer, we silenced its expression in two pancreatic cancer cell lines (Panc1 and MiaPaCa) by stable transfection of a c-Myb-targeted short-hairpin RNA (shRNA)-expression plasmid. Silencing of c-Myb expression resulted in diminished growth and clonogenicity of pancreatic cancer cells. c-Myb knockdown pancreatic cancer cells were arrested at G1/S boundary of cell cycle, and exhibited enhanced apoptosis. Furthermore, we observed decreased migration and invasion in c-Myb silenced pancreatic cancer cells as compared to the control cells. Immunoblot analysis demonstrated gain of epithelial- and loss of mesenchymal- markers in c-Myb knockdown pancreatic cancer cells, thus indicating a reversal of epithelial to mesenchymal transition (EMT). We also observed noticeable changes in cell morphology and actin-organization upon silencing of c-Myb expression that were consistent with loss of mesenchymal features. Together, these findings provide first experimental evidence for a functional role of c-Myb in pancreatic cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4011. doi:10.1158/1538-7445.AM2011-4011