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- Raju V. Pusapati
- Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, Science Park Research Division, Smithville, TX 78957; Division of Pharmacology and Toxicology, University of Texas, Austin, TX 78712; and Department of Veterinary Sciences, University of Texas M. D. Anderson Cancer Center, Bastrop, TX 78602
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- Robert J. Rounbehler
- Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, Science Park Research Division, Smithville, TX 78957; Division of Pharmacology and Toxicology, University of Texas, Austin, TX 78712; and Department of Veterinary Sciences, University of Texas M. D. Anderson Cancer Center, Bastrop, TX 78602
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- SungKi Hong
- Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, Science Park Research Division, Smithville, TX 78957; Division of Pharmacology and Toxicology, University of Texas, Austin, TX 78712; and Department of Veterinary Sciences, University of Texas M. D. Anderson Cancer Center, Bastrop, TX 78602
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- John T. Powers
- Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, Science Park Research Division, Smithville, TX 78957; Division of Pharmacology and Toxicology, University of Texas, Austin, TX 78712; and Department of Veterinary Sciences, University of Texas M. D. Anderson Cancer Center, Bastrop, TX 78602
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- Mingshan Yan
- Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, Science Park Research Division, Smithville, TX 78957; Division of Pharmacology and Toxicology, University of Texas, Austin, TX 78712; and Department of Veterinary Sciences, University of Texas M. D. Anderson Cancer Center, Bastrop, TX 78602
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- Kaoru Kiguchi
- Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, Science Park Research Division, Smithville, TX 78957; Division of Pharmacology and Toxicology, University of Texas, Austin, TX 78712; and Department of Veterinary Sciences, University of Texas M. D. Anderson Cancer Center, Bastrop, TX 78602
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- Mark J. McArthur
- Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, Science Park Research Division, Smithville, TX 78957; Division of Pharmacology and Toxicology, University of Texas, Austin, TX 78712; and Department of Veterinary Sciences, University of Texas M. D. Anderson Cancer Center, Bastrop, TX 78602
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- Paul K. Wong
- Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, Science Park Research Division, Smithville, TX 78957; Division of Pharmacology and Toxicology, University of Texas, Austin, TX 78712; and Department of Veterinary Sciences, University of Texas M. D. Anderson Cancer Center, Bastrop, TX 78602
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- David G. Johnson
- Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, Science Park Research Division, Smithville, TX 78957; Division of Pharmacology and Toxicology, University of Texas, Austin, TX 78712; and Department of Veterinary Sciences, University of Texas M. D. Anderson Cancer Center, Bastrop, TX 78602
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説明
<jats:p>Overexpression of the<jats:italic>c-myc</jats:italic>oncogene contributes to the development of a significant number of human cancers. In response to deregulated Myc activity, the p53 tumor suppressor is activated to promote apoptosis and inhibit tumor formation. Here we demonstrate that p53 induction in response to Myc overexpression requires the ataxia-telangiectasia mutated (ATM) kinase, a major regulator of the cellular response to DNA double-strand breaks. In a transgenic mouse model overexpressing Myc in squamous epithelial tissues, inactivation of<jats:italic>Atm</jats:italic>suppresses apoptosis and accelerates tumorigenesis. Deregulated Myc expression induces DNA damage in primary transgenic keratinocytes and the formation of γH2AX and phospho-SMC1 foci in transgenic tissue. These findings suggest that Myc overexpression causes DNA damage<jats:italic>in vivo</jats:italic>and that the ATM-dependent response to this damage is critical for p53 activation, apoptosis, and the suppression of tumor development.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 103 (5), 1446-1451, 2006-01-23
Proceedings of the National Academy of Sciences
