We here establish a mouse cancer model called Multi-Hit that allows for the evaluation of oncogene cooperativities in tumor development. The model is based on the stochastic expression of oncogene combinations ("hits") that are mediated by Cre in a given tissue. Cells with cooperating hits are positively selected and give rise to tumors. We used this approach to evaluate the requirement of Ras downstream effector pathways in tumorigenesis.
Animals Disease Models, Animal* Female Lung Neoplasms/genetics Lung Neoplasms/metabolism* Lung Neoplasms/pathology Male Mice Mice, Transgenic Neoplasms, Experimental/genetics Neoplasms, Experimental/metabolism* Neoplasms, Experimental/pathology Oncogene Protein p21(ras)/genetics Oncogene Protein p21(ras)/metabolism* Pancreatic Neoplasms/genetics Pancreatic Neoplasms/metabolism Pancreatic Neoplasms/pathology Signal Transduction*/genetics