Abstract
Mice engineered with G12D versus Q61R mutant of Kras exhibit differences in the number and grade of tumors. Namely, the incidence or grade of oral or forestomach squamous epithelial lesions was more prevalent in the KrasG12D background while hematolymphopoietic disease was more prevalent in the KrasQ61R background. Loss of the Trp53 gene encoding p53 enhances the ability of oncogenic Kras to initiate tumorigenesis in carcinogen and genetic models of lung cancer, while an extra copy of Trp53 (Super p53) was recently shown to suppress Kras-induced tumorigenesis in a genetic model of this disease. Given this, we evaluated whether such an extra copy of Trp53 would alter tumorigenesis upon global activation of a modified Kras allele engineered with either a G12D or Q61R mutation. We report that an increase in p53 dosage generally reduced tumor number or grade across a number of organs in a manner largely independent of the type of Kras mutation, which was sufficient to extend lifespan in the less aggressive background of a KrasG12D initiating mutation.
Competing Interest Statement
The authors have declared no competing interest.
