| First Author | Young NP | Year | 2011 |
| Journal | Cancer Res | Volume | 71 |
| Issue | 11 | Pages | 4040-7 |
| PubMed ID | 21512139 | Mgi Jnum | J:172206 |
| Mgi Id | MGI:5004997 | Doi | 10.1158/0008-5472.CAN-10-4563 |
| Citation | Young NP, et al. (2011) Uncoupling Cancer Mutations Reveals Critical Timing of p53 Loss in Sarcomagenesis. Cancer Res 71(11):4040-7 |
| abstractText | 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-ras(G12D) 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-ras(G12D) 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. (c)2011 AACR. |
