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Publication : Smoking, p53 mutation, and lung cancer.

First Author  Gibbons DL Year  2014
Journal  Mol Cancer Res Volume  12
Issue  1 Pages  3-13
PubMed ID  24442106 Mgi Jnum  J:208153
Mgi Id  MGI:5561175 Doi  10.1158/1541-7786.MCR-13-0539
Citation  Gibbons DL, et al. (2014) Smoking, p53 mutation, and lung cancer. Mol Cancer Res 12(1):3-13
abstractText  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.
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