Cancer Research Cancer Health Disparities Conference 2009
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 Zhao, Y.
Right arrow Articles by St. Clair, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhao, Y.
Right arrow Articles by St. Clair, D.
[Cancer Research 61, 6082-6088, August 15, 2001]
© 2001 American Association for Cancer Research

Carcinogenesis

Overexpression of Manganese Superoxide Dismutase Suppresses Tumor Formation by Modulation of Activator Protein-1 Signaling in a Multistage Skin Carcinogenesis Model1

Yunfeng Zhao, Yi Xue, Terry D. Oberley, Kelley K. Kiningham, Shu-Mei Lin, Hsiu-Chuan Yen2, Hideyuki Majima3, Judy Hines and Daret St. Clair4

Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40536 [Y. Z., K. K. K., S-M. L., H-C. Y., H. M., J. H., D. S. C.], and Department of Pathology [Y. X., T. D. O.] and Veterans Affairs Hospital [T. D. O.], University of Wisconsin, Madison, Wisconsin 53705

Manganese superoxide dismutase (MnSOD) is a nuclear encoded primary antioxidant enzyme localized in mitochondria. Because expression of MnSOD plays a major role in maintaining cellular redox status and reactive oxygen species are known to play a role in signal transduction and carcinogenesis, we investigated the role of MnSOD in the development of cancer using a two-stage [7,12-dimethylbenz(a)-anthracene plus 12-O-tetradecanoylphorbol-13-acetate (TPA)] skin carcinogenesis model. Female transgenic mice expressing the human MnSOD gene in the skin and their nontransgenic counterparts were used in this study. Pathological examination demonstrated significant reduction of papilloma formation in transgenic mice. Quantitative analysis of 4-hydroxy-2-nonenal-modified proteins showed greater accumulation of oxidative damage products in nontransgenic compared with transgenic mice, and this oxidative damage was demonstrated to be present in both mitochondria and nucleus. TPA increased activator protein-1 (AP-1) binding activity within 6 h in nontransgenic mice, but increased AP-1 binding activity was delayed in the transgenic mice. Electrophoretic mobility shift assay, transcription of the target genes, and Western analysis studies indicated that the increased AP-1 binding activity was attributable to induction of the Jun but not the Fos protein families. Overexpression of MnSOD selectively inhibited the TPA-induced activation of protein kinase C{epsilon} and prevented subsequent activation of c-Jun NH2-terminal kinase in response to TPA. Overall, these results indicate that MnSOD regulates both cellular redox status and selectively modulates PKC{epsilon} signaling, thereby delaying AP-1 activation and inhibiting tumor promotion, resulting in reduction of tumors in MnSOD transgenic mice.




This article has been cited by other articles:


Home page
 CarcinogenesisHome page
S. Dey, V. Bakthavatchalu, M. T. Tseng, P. Wu, R. L. Florence, E. A. Grulke, R. A. Yokel, S. K. Dhar, H.-S. Yang, Y. Chen, et al.
Interactions between SIRT1 and AP-1 reveal a mechanistic insight into the growth promoting properties of alumina (Al2O3) nanoparticles in mouse skin epithelial cells
Carcinogenesis, October 1, 2008; 29(10): 1920 - 1929.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
C. Tang, B. T. Ang, and S. Pervaiz
Cancer stem cell: target for anti-cancer therapy
FASEB J, December 1, 2007; 21(14): 3777 - 3785.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
S. K. Dhar, Y. Xu, T. Noel, and D. K. St Clair
Chronic exposure to 12-O-tetradecanoylphorbol-13-acetate represses sod2 induction in vivo: the negative role of p50
Carcinogenesis, December 1, 2007; 28(12): 2605 - 2613.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Biol.Home page
Q. Gu, G. T. Bowden, D. Normolle, and Y. Sun
SAG/ROC2 E3 ligase regulates skin carcinogenesis by stage-dependent targeting of c-Jun/AP1 and I{kappa}B-{alpha}/NF-{kappa}B
J. Cell Biol., September 7, 2007; 178(6): 1009 - 1023.
[Abstract] [Full Text] [PDF]

Home page
 MutagenesisHome page
G. J.Kim, K. Chandrasekaran, and W. F.Morgan
Mitochondrial dysfunction, persistently elevated levels of reactive oxygen species and radiation-induced genomic instability: a review
Mutagenesis, November 1, 2006; 21(6): 361 - 367.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
Y. Zhao, L. Chaiswing, V. Bakthavatchalu, T. D. Oberley, and D. K. St. Clair
Ras mutation promotes p53 activation and apoptosis of skin keratinocytes
Carcinogenesis, August 1, 2006; 27(8): 1692 - 1698.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
C. van Waveren, Y. Sun, H. S. Cheung, and C. T. Moraes
Oxidative phosphorylation dysfunction modulates expression of extracellular matrix--remodeling genes and invasion
Carcinogenesis, March 1, 2006; 27(3): 409 - 418.
[Abstract] [Full Text] [PDF]

Home page
 Arch SurgHome page
B. Hermann, Y. Li, M. B. Ray, J. M. Wo, and R. C. G. Martin II
Association of Manganese Superoxide Dismutase Expression With Progression of Carcinogenesis in Barrett Esophagus
Arch Surg, December 1, 2005; 140(12): 1204 - 1209.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
Y.-J. Surh, J. K. Kundu, H.-K. Na, and J.-S. Lee
Redox-Sensitive Transcription Factors as Prime Targets for Chemoprevention with Anti-Inflammatory and Antioxidative Phytochemicals
J. Nutr., December 1, 2005; 135(12): 2993S - 3001S.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Y. Zhao, L. Chaiswing, J. M. Velez, I. Batinic-Haberle, N. H. Colburn, T. D. Oberley, and D. K. St. Clair
p53 Translocation to Mitochondria Precedes Its Nuclear Translocation and Targets Mitochondrial Oxidative Defense Protein-Manganese Superoxide Dismutase
Cancer Res., May 1, 2005; 65(9): 3745 - 3750.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Y. Zhao, L. Chaiswing, T. D. Oberley, I. Batinic-Haberle, W. St. Clair, C. J. Epstein, and D. St. Clair
A Mechanism-Based Antioxidant Approach for the Reduction of Skin Carcinogenesis
Cancer Res., February 15, 2005; 65(4): 1401 - 1405.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
S. Yang and F. L. Meyskens Jr.
Alterations in Activating Protein 1 Composition Correlate with Phenotypic Differentiation Changes Induced by Resveratrol in Human Melanoma
Mol. Pharmacol., January 1, 2005; 67(1): 298 - 308.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
D. St. Clair
Manganese Superoxide Dismutase: Genetic Variation and Regulation
J. Nutr., November 1, 2004; 134(11): 3190S - 3191S.
[Full Text] [PDF]

Home page
 CarcinogenesisHome page
D.-X. Hou, K. Kai, J.-J. Li, S. Lin, N. Terahara, M. Wakamatsu, M. Fujii, M. R. Young, and N. Colburn
Anthocyanidins inhibit activator protein 1 activity and cell transformation: structure-activity relationship and molecular mechanisms
Carcinogenesis, January 1, 2004; 25(1): 29 - 36.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
A. Dhar, J. M. Brindley, C. Stark, M. L. Citro, L. K. Keefer, and N. H. Colburn
Nitric oxide does not mediate but inhibits transformation and tumor phenotype
Mol. Cancer Ther., December 1, 2003; 2(12): 1285 - 1293.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
V. L. Kinnula and J. D. Crapo
Superoxide Dismutases in the Lung and Human Lung Diseases
Am. J. Respir. Crit. Care Med., June 15, 2003; 167(12): 1600 - 1619.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
T. D. Oberley
Oxidative Damage and Cancer
Am. J. Pathol., February 1, 2002; 160(2): 403 - 408.
[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 © 2001 by the American Association for Cancer Research.