Kim Michael Paul, Zhang Yun, Lozano Guillermina
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center , Houston, TX , USA ; Department of Genetics, The University of Texas MD Anderson Cancer Center , Houston, TX , USA.
Department of Genetics, The University of Texas MD Anderson Cancer Center , Houston, TX , USA.
Front Oncol. 2015 Nov 11;5:249. doi: 10.3389/fonc.2015.00249. eCollection 2015.
The functional importance of p53 as a tumor suppressor gene is evident through its pervasiveness in cancer biology. The p53 gene is the most commonly altered gene in human cancer; however, not all genetic alterations are biologically equivalent. The majority of alterations involve p53 missense mutations that result in the production of mutant p53 proteins. Such mutant p53 proteins lack normal p53 function and may concomitantly gain novel functions, often with deleterious effects. Here, we review characterized mechanisms of mutant p53 gain of function in various model systems. In addition, we review mutant p53 addiction as emerging evidence suggests that tumors may depend on sustained mutant p53 activity for continued growth. We also discuss the role of p53 in stromal elements and their contribution to tumor initiation and progression. Lastly, current genetic mouse models of mutant p53 in various organ systems are reviewed and their limitations discussed.
p53作为一种肿瘤抑制基因的功能重要性，通过其在癌症生物学中的普遍性得以体现。p53基因是人类癌症中最常发生改变的基因；然而，并非所有的基因改变在生物学上都是等同的。大多数改变涉及p53错义突变，这些突变导致突变型p53蛋白的产生。此类突变型p53蛋白缺乏正常p53功能，并且可能同时获得新功能，通常具有有害影响。在此，我们综述了各种模型系统中已明确的突变型p53功能获得机制。此外，鉴于新出现的证据表明肿瘤可能依赖持续的突变型p53活性来持续生长，我们对突变型p53成瘾现象进行了综述。我们还讨论了p53在基质成分中的作用及其对肿瘤起始和进展的贡献。最后，我们综述了目前各种器官系统中突变型p53的基因小鼠模型，并讨论了它们的局限性。
