Smoking, p53 mutation, and lung cancer.
Smoking, p53 mutation, and lung cancer.
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DOI：
10.1158/1541-7786.mcr-13-0539
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发表时间：
2014-01
期刊：
影响因子：
--
通讯作者：
Kurie JM
中科院分区：
文献类型：
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作者：
Gibbons DL;Byers LA;Kurie JM
这是美国卫生局局长关于吸烟与健康的报告发表50周年。也许没有其他单一事件更能突出吸烟对癌症发展的影响。烟草暴露是口腔、传导性气道和肺部癌症的主要原因。由于烟草烟雾中的许多致癌物质，吸烟相关的恶性肿瘤具有高基因组范围的突变负担，包括编码p53的基因。p53蛋白是癌症中最常见的突变肿瘤抑制因子，负责一系列因突变而受损的关键细胞功能。在此，我们回顾烟草暴露和癌症之间的流行病学联系，p53突变在肺癌中的分子基础，和正常的分子和细胞的作用，p53被废除在肺肿瘤的发展和进展过程中定义的体外和体内研究。我们还考虑在临床环境中的突变型p53的细胞作用和遗传小鼠模型的数据为基础的靶向突变型p53的治疗潜力。
This issue marks the 50th Anniversary of the release of the U.S. Surgeon General’s Report on Smoking and Health. Perhaps no other singular event has done more to highlight the effects of smoking on the development of cancer. Tobacco exposure is the leading cause of cancers involving the oral cavity, conductive airways and the lung. Owing to the many carcinogens in tobacco smoke, smoking-related malignancies have a high genome-wide burden of mutations, including in the gene encoding for p53. The p53 protein is the most frequently mutated tumor suppressor in cancer, responsible for a range of critical cellular functions that are compromised by the presence of a mutation. Herein we review the epidemiologic connection between tobacco exposure and cancer, the molecular basis of p53 mutation in lung cancer, and the normal molecular and cellular roles of p53 that are abrogated during lung tumor development and progression as defined by in vitro and in vivo studies. We also consider the therapeutic potential of targeting mutant p53 in a clinical setting based upon the cellular role of mutant p53 and data from genetic murine models.