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Supplementary Figure 2 from Uncoupling Cancer Mutations Reveals Critical Timing of p53 Loss in Sarcomagenesis

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posted on 2023-03-30, 21:32 authored by Nathan P. Young, Denise Crowley, Tyler Jacks
Supplementary Figure 2 from Uncoupling Cancer Mutations Reveals Critical Timing of p53 Loss in Sarcomagenesis

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ARTICLE ABSTRACT

It is well accepted that cancer develops following the sequential accumulation of multiple alterations, but how the temporal order of events affects tumor initiation and/or progression remains largely unknown. Here, we describe a mouse model that allows for temporally distinct cancer mutations. By integrating a Flp-inducible allele of K-rasG12D with established methods for Cre-mediated p53 deletion, we were able to separately control the mutation of these commonly associated cancer genes in vitro and in vivo. We show that delaying p53 deletion relative to K-rasG12D activation reduced tumor burden in a mouse model of soft-tissue sarcoma, suggesting that p53 strongly inhibits very early steps of transformation in the muscle. Furthermore, using in vivo RNA interference, we implicate the p53 target gene p21 as a critical mediator in this process, highlighting cell-cycle arrest as an extremely potent tumor suppressor mechanism. Cancer Res; 71(11); 4040–7. ©2011 AACR.

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