RCAS-mediated retroviral gene delivery: a versatile tool for the study of gene function in a mouse model of pancreatic cancer.

Pancreatic cancer is one of the most common causes of cancer death in Western civilization and the 5-year survival rate is below 5%. To improve the prognosis of pancreatic cancer, there is the need to develop effective nonsurgical treatment options for the disease. In particular, in vivo models to validate potential targets at the genetic level are required. In this study we demonstrate that RCAS-mediated retroviral gene transfer into orthotopic pancreatic cancer tumor grafts is feasible. Furthermore, we show effective RCAS-dependent RNA interference in vivo. We validate in vivo bioluminescence imaging as a reliable tool to monitor tumor progression of orthotopic pancreatic cancer transplants longitudinally. In addition, we show that restoring expression of the tumor suppressor p53 by RCAS-mediated gene transfer and knockdown of the epidermal growth factor receptor by RCAS-dependent RNA interference impairs orthotopic pancreatic tumor growth in vivo. In conclusion, these data demonstrate that combining in vivo bioluminescence imaging with RCAS-mediated gene or short hairpin RNA transfer is a new model to investigate gene function in pancreatic cancer grafts and allows validation of potential new drug targets in vivo.