Cancer Research CTRC-AACR San Antonio Breast Cancer Symposium AACR Conference on Molecular Diagnostics - 2008
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Xie, Y.
Right arrow Articles by Miller, J. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xie, Y.
Right arrow Articles by Miller, J. H.
[Cancer Research 64, 3096-3102, May 1, 2004]
© 2004 American Association for Cancer Research

Regular Articles

Deficiencies in Mouse Myh and Ogg1 Result in Tumor Predisposition and G to T Mutations in Codon 12 of the K-Ras Oncogene in Lung Tumors

Yali Xie1, Hanjing Yang1, Cristina Cunanan1, Kimberly Okamoto1, Darryl Shibata2, Janet Pan1, Deborah E. Barnes3, Tomas Lindahl3, Michael McIlhatton4, Richard Fishel4 and Jeffrey H. Miller1

1 Department of Microbiology, Immunology, and Molecular Genetics and the Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California; 2 Department of Pathology, University of Southern California, School of Medicine, Los Angeles, California; 3 Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts, United Kingdom; and 4 Department of Microbiology and Immunology, Genetics and Molecular Biology Program, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania

Oxidative DNA damage is unavoidably and continuously generated by oxidant byproducts of normal cellular metabolism. The DNA damage repair genes, mutY and mutM, prevent G to T mutations caused by reactive oxygen species in Escherichia coli, but it has remained debatable whether deficiencies in their mammalian counterparts, Myh and Ogg1, are directly involved in tumorigenesis. Here, we demonstrate that deficiencies in Myh and Ogg1 predispose 65.7% of mice to tumors, predominantly lung and ovarian tumors, and lymphomas. Remarkably, subsequent analyses identified G to T mutations in 75% of the lung tumors at an activating hot spot, codon 12, of the K-ras oncogene, but none in their adjacent normal tissues. Moreover, malignant lung tumors were increased with combined heterozygosity of Msh2, a mismatch repair gene involved in oxidative DNA damage repair as well. Thus, oxidative DNA damage appears to play a causal role in tumorigenesis, and codon 12 of K-ras is likely to be an important downstream target in lung tumorigenesis. The multiple oxidative repair genes are required to prevent mutagenesis and tumor formation. The mice described here provide a valuable model for studying the mechanisms of oxidative DNA damage in tumorigenesis and investigating preventive or therapeutic approaches.




This article has been cited by other articles:


Home page
 Cancer Res.Home page
E. Larsen, L. Kleppa, T. J. Meza, L. A. Meza-Zepeda, C. Rada, C. G. Castellanos, G. F. Lien, G. J. Nesse, M. S. Neuberger, J. K. Laerdahl, et al.
Early-Onset Lymphoma and Extensive Embryonic Apoptosis in Two Domain-Specific Fen1 Mice Mutants
Cancer Res., June 15, 2008; 68(12): 4571 - 4579.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. Ringvoll, M. N. Moen, L. M. Nordstrand, L. B. Meira, B. Pang, A. Bekkelund, P. C. Dedon, S. Bjelland, L. D. Samson, P. O. Falnes, et al.
AlkB Homologue 2-Mediated Repair of Ethenoadenine Lesions in Mammalian DNA
Cancer Res., June 1, 2008; 68(11): 4142 - 4149.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
Y. Xie, H. Yang, J. H. Miller, D. M. Shih, G. G. Hicks, J. Xie, and R. P. Shiu
Cells deficient in oxidative DNA damage repair genes Myh and Ogg1 are sensitive to oxidants with increased G2/M arrest and multinucleation
Carcinogenesis, April 1, 2008; 29(4): 722 - 728.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. Sakamoto, Y. Tominaga, K. Yamauchi, Y. Nakatsu, K. Sakumi, K. Yoshiyama, A. Egashira, S. Kura, T. Yao, M. Tsuneyoshi, et al.
MUTYH-Null Mice Are Susceptible to Spontaneous and Oxidative Stress Induced Intestinal Tumorigenesis
Cancer Res., July 15, 2007; 67(14): 6599 - 6604.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. Trapp, M. Schwarz, and B. Epe
The Peroxisome Proliferator WY-14,643 Promotes Hepatocarcinogenesis Caused by Endogenously Generated Oxidative DNA Base Modifications in Repair-Deficient Csbm/m/Ogg1-/- Mice
Cancer Res., June 1, 2007; 67(11): 5156 - 5161.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
P. Bonde, D. Gao, L. Chen, T. Miyashita, E. Montgomery, J. W. Harmon, and C. Wei
Duodenal Reflux Leads to Down Regulation of DNA Mismatch Repair Pathway in an Animal Model of Esophageal Cancer
Ann. Thorac. Surg., February 1, 2007; 83(2): 433 - 440.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Landi, F. Gemignani, F. Canzian, V. Gaborieau, R. Barale, D. Landi, N. Szeszenia-Dabrowska, D. Zaridze, J. Lissowska, P. Rudnai, et al.
DNA Repair and Cell Cycle Control Genes and the Risk of Young-Onset Lung Cancer.
Cancer Res., November 15, 2006; 66(22): 11062 - 11069.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
H. J. Thompson
Oxidative DNA Damage and Cancer Risk Assessment
J. Nutr., October 1, 2006; 136(10): 2693S - 2694S.
[Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
G. F. Barker, N. D. Manzo, K. L. Cotich, R. K. Shone, and A. B. Waxman
DNA Damage Induced by Hyperoxia: Quantitation and Correlation with Lung Injury
Am. J. Respir. Cell Mol. Biol., September 1, 2006; 35(3): 277 - 288.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
J. W. Hill and M. K. Evans
Dimerization and opposite base-dependent catalytic impairment of polymorphic S326C OGG1 glycosylase
Nucleic Acids Res., March 20, 2006; 34(5): 1620 - 1632.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
P. Macpherson, F. Barone, G. Maga, F. Mazzei, P. Karran, and M. Bignami
8-Oxoguanine incorporation into DNA repeats in vitro and mismatch recognition by MutS{alpha}
Nucleic Acids Res., September 20, 2005; 33(16): 5094 - 5105.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. C. Hollander, R. T. Philburn, A. D. Patterson, S. Velasco-Miguel, E. C. Friedberg, R. I. Linnoila, and A. J. Fornace Jr.
Deletion of XPC leads to lung tumors in mice and is associated with early events in human lung carcinogenesis
PNAS, September 13, 2005; 102(37): 13200 - 13205.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
J. Hu, S. Z. Imam, K. Hashiguchi, N. C. de Souza-Pinto, and V. A. Bohr
Phosphorylation of human oxoguanine DNA glycosylase ({alpha}-OGG1) modulates its function
Nucleic Acids Res., June 7, 2005; 33(10): 3271 - 3282.
[Abstract] [Full Text] [PDF]

Home page
 Sci Aging Knowl EnvironHome page
A. M. Skinner and M. S. Turker
Oxidative Mutagenesis, Mismatch Repair, and Aging
Sci. Aging Knowl. Environ., March 2, 2005; 2005(9): re3 - re3.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
H. Bai, S.ân Jones, X. Guan, T. M. Wilson, J. R. Sampson, J. P. Cheadle, and A-L. Lu
Functional characterization of two human MutY homolog (hMYH) missense mutations (R227W and V232F) that lie within the putative hMSH6 binding domain and are associated with hMYH polyposis
Nucleic Acids Res., January 26, 2005; 33(2): 597 - 604.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
O. M. Sieber, K. M. Howarth, C. Thirlwell, A. Rowan, N. Mandir, R. A. Goodlad, A. Gilkar, B. Spencer-Dene, G. Stamp, V. Johnson, et al.
Myh Deficiency Enhances Intestinal Tumorigenesis in Multiple Intestinal Neoplasia (ApcMin/+) Mice
Cancer Res., December 15, 2004; 64(24): 8876 - 8881.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
K. Hashimoto, Y. Tominaga, Y. Nakabeppu, and M. Moriya
Futile short-patch DNA base excision repair of adenine:8-oxoguanine mispair
Nucleic Acids Res., November 5, 2004; 32(19): 5928 - 5934.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
M. de Padula, G. Slezak, P. Auffret van Der Kemp, and S. Boiteux
The post-replication repair RAD18 and RAD6 genes are involved in the prevention of spontaneous mutations caused by 7,8-dihydro-8-oxoguanine in Saccharomyces cerevisiae
Nucleic Acids Res., September 23, 2004; 32(17): 5003 - 5010.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. T. Russo, G. De Luca, P. Degan, E. Parlanti, E. Dogliotti, D. E. Barnes, T. Lindahl, H. Yang, J. H. Miller, and M. Bignami
Accumulation of the Oxidative Base Lesion 8-Hydroxyguanine in DNA of Tumor-Prone Mice Defective in Both the Myh and Ogg1 DNA Glycosylases
Cancer Res., July 1, 2004; 64(13): 4411 - 4414.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2004 by the American Association for Cancer Research.