| First Author | Slatter TL | Year | 2011 |
| Journal | Blood | Volume | 117 |
| Issue | 19 | Pages | 5166-77 |
| PubMed ID | 21411755 | Mgi Jnum | J:173271 |
| Mgi Id | MGI:5013697 | Doi | 10.1182/blood-2010-11-321851 |
| Citation | Slatter TL, et al. (2011) Hyperproliferation, cancer, and inflammation in mice expressing a Delta133p53-like isoform. Blood 117(19):5166-77 |
| abstractText | The p53 protein is a pivotal tumor suppressor that is frequently mutated in many human cancers, although precisely how p53 prevents tumors is still unclear. To add to its complexity, several isoforms of human p53 have now been reported. The Delta133p53 isoform is generated from an alternative transcription initiation site in intron 4 of the p53 gene (Tp53) and lacks the N-terminus. Elevated levels of Delta133p53 have been observed in a variety of tumors. To explore the functions of Delta133p53, we created a mouse expressing an N-terminal deletion mutant of p53 (Delta122p53) that corresponds to Delta133p53. Delta122p53 mice show decreased survival and a different and more aggressive tumor spectrum compared with p53 null mice, implying that Delta122p53 is a dominant oncogene. Consistent with this, Delta122p53 also confers a marked proliferative advantage on cells and reduced apoptosis. In addition to tumor development, Delta122p53 mice show a profound proinflammatory phenotype having increased serum concentrations of interleukin-6 and other proinflammatory cytokines and lymphocyte aggregates in the lung and liver as well as other pathologies. Based on these observations, we propose that human Delta133p53 also functions to promote cell proliferation and inflammation, one or both of which contribute to tumor development. |
