Absence of p53 in a Mouse Mammary Tumor Model Promotes Tumor Cell Proliferation without Affecting Apoptosis1

Loss or mutation of p53 may have multiple biological and genetic effects that result in accelerated tumor progression. Loss of p53 in some tumors has been correlated with a marked decrease in tumor cell apoptosis. p53 loss may also accelerate tumor growth through an increase in cell proliferation rates. To examine the effects of p53 loss on tumor progression in a controlled experimental context, we previously crossed p53-deficient mice to mammary tumor-susceptible Wnt-1 transgenic (TG) mice. The resulting female Wnt-1 TG offspring of this cross all developed mammary tumors, regardless of p53 status (p53+1+, p53+/, or p53-/-). However, female p53-/- Wnt-1 TG mice developed tumors much sooner than thei