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Age‐dependent expression of cancer‐related genes in a long‐lived seabird

机译:在长期的海鸟中依赖于癌症相关基因的年龄依赖性表达

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摘要

Studies of model animals like mice and rats have led to great advances in our understanding of the process of tumorigenesis, but this line of study has less to offer for understanding the mechanisms of cancer resistance. Increasing the diversity of nonmodel species from the perspective of molecular mechanisms of natural cancer resistance can lead to new insights into the evolution of protective mechanisms against neoplastic processes and to a wider understanding of natural cancer defense mechanisms. Such knowledge could then eventually be harnessed for the development of human cancer therapies. We suggest here that seabirds are promising, albeit currently completely ignored candidates for studying cancer defense mechanisms, as they have a longer maximum life span than expected from their body size and rates of energy metabolism and may have thus evolved mechanisms to limit neoplasia progression, especially at older ages. We here apply a novel, intraspecific approach of comparing old and young seabirds for improving our understanding of aging and neoplastic processes in natural settings. We used the long‐lived common gulls ( ) for studying the age‐related pattern of expression of cancer‐related genes, based on transcriptome analysis and databases of orthologues of human cancer genes. The analysis of differently expressed cancer‐related genes between young and old gulls indicated that similarly to humans, age is potentially affecting cancer risk in this species. Out of eleven differentially expressed cancer‐related genes between the groups, three were likely artifactually linked to cancer. The remaining eight were downregulated in old gulls compared to young ones. The downregulation of five of them could be interpreted as a mechanism suppressing neoplasia risk and three as increasing the risk. Based on these results, we suggest that old gulls differ from young ones both from the aspect of cancer susceptibility and tumor suppression at the genetic level.
机译:对小鼠和大鼠等模型动物的研究导致了我们对肿瘤内酯过程的理解的巨大进步,但这种研究较少旨在理解癌症抵抗力的机制。从天然癌症抗性的分子机制的角度提高非典范物种的多样性,可以导致新的见解对肿瘤过程的保护机制的演变和对自然癌症防御机制的更广泛了解。然后,这些知识最终可以利用人类癌症疗法的发展。我们建议在这里,海鸟是有希望的,虽然目前完全被忽视了学习癌症防御机制的候选人,因为它们具有比其体尺寸和能量新陈代谢的最高寿命和能量新陈代谢的最高寿命,因此可能会产生限制肿瘤进展的机制,特别是年龄较大。我们在这里采用了一种比较旧和年轻海鸟来改善我们对自然环境中老化和肿瘤过程的理解的新颖。我们使用了长期的常见鸥()用于研究与人类癌症基因的转录组分分析和数据库的转录组分析和数据库相关的癌症相关基因的年龄相关的表达模式。对年轻和古老的鸥之间的不同表达癌症相关基因的分析表明,与人类同样,年龄可能会影响该物种中的癌症风险。在11个差异表达癌症相关基因中,三种可能与癌症有关。与年轻人相比,剩下的八个在旧海鸥中下调。其中五种的下调可以被解释为抑制肿瘤风险的机制,三是增加风险。基于这些结果,我们建议从癌症水平的癌症易感性和肿瘤抑制方面与旧鸥不同。

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