Long-lived cancer-resistant rodents as new model species for cancer research.
Long-lived cancer-resistant rodents as new model species for cancer research.
复制标题
DOI：
10.3389/fgene.2012.00319
复制
发表时间：
2012
影响因子：
3.7
通讯作者：
Seluanov A
中科院分区：
文献类型：
--
作者：
Azpurua J;Seluanov A
大多数啮齿动物体型小，寿命短，但有几个谱系独立地进化出了长寿命，而没有伴随着体重的增加。最值得注意的是两种地下物种裸鼹鼠（NMR）和盲鼹鼠（BMR），它们的最长寿命分别为32年和21年。这些物种的长寿引发了人们对肿瘤抑制策略的兴趣，这些策略可能也已经进化，因为对于许多啮齿动物物种（包括小鼠，大鼠，豚鼠，沙鼠和仓鼠）来说，肿瘤是晚年死亡的主要来源。在这里，我们回顾了最近的文献抗癌机制在长寿啮齿动物。NMR和BMR似乎都开发了依赖于细胞外信号的肿瘤防御。然而，虽然NMR依赖于一种形式的接触抑制来抑制生长，但BMR进化出一种由干扰素释放和快速坏死细胞死亡介导的机制。尽管这两种生物最终都依赖于典型的下游肿瘤抑制因子（pRB和p53），但研究表明，物种可以进化出不同的策略来实现肿瘤抗性。重要的是，如果这些机制可以在人类细胞中激活，对这些抗癌啮齿动物的研究可能有益于人类健康。
Most rodents are small and short-lived, but several lineages have independently evolved long lifespans without a concomitant increase in body-mass. Most notable are the two subterranean species naked mole rat (NMR) and blind mole rat (BMR) which have maximum lifespans of 32 and 21 years, respectively. The longevity of these species has sparked interest in the tumor suppression strategies that may have also evolved, because for many rodent species (including mice, rats, guinea pigs, gerbils, and hamsters) tumors are a major source of late-life mortality. Here, we review the recent literature on anti-cancer mechanisms in long-lived rodents. Both NMR and BMR seem to have developed tumor defenses that rely on extra-cellular signals. However, while the NMR relies on a form of contact inhibition to suppress growth, the BMR evolved a mechanism mediated by the release of interferon, and rapid necrotic cell death. Although both organisms ultimately rely on canonical downstream tumor suppressors (pRB and p53) the studies reveal species can evolve different strategies to achieve tumor-resistance. Importantly, studies of these cancer-resistant rodents may benefit human health if such mechanisms can be activated in human cells.