Skip Navigation


Carcinogenesis Advance Access originally published online on April 12, 2006
Carcinogenesis 2006 27(8):1692-1698; doi:10.1093/carcin/bgl037
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
27/8/1692    most recent
bgl037v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (4)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Zhao, Y.
Right arrow Articles by St. Clair, D. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhao, Y.
Right arrow Articles by St. Clair, D. K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Ras mutation promotes p53 activation and apoptosis of skin keratinocytes

Yunfeng Zhao1,5, Luksana Chaiswing2,4, Vasudevan Bakthavatchalu1, Terry D. Oberley2,3 and Daret K. St. Clair1,*

1 Graduate Center for Toxicology, University of Kentucky Lexington, KY 40536, USA
2 Department of Pathology, University of Wisconsin Madison, WI 53705, USA
3 VA Hospital, University of Wisconsin Madison, WI 53705, USA
4 Faculty of Medical Technology, Mahidol University Bangkok, Thailand 10700
5 Department of Pharmacology, Toxicology & Neuroscience, LSU Health Science Center Shreveport, LA 71103, USA

*To whom correspondence should be addressed. Tel: +1 859 257 3956; Fax: +1 859 323 1059; Email: dstcl00{at}pop.uky.edu

Previous studies in our laboratory demonstrated that 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate (DMBA/TPA) treatment induced apoptosis and mitochondrial translocation of the tumor suppressor p53 in a mouse skin carcinogenesis model, suggesting that oncogenic versus cell death signaling involve a common mediator. Mutational activation of oncogenic Ras is an early event and has been demonstrated to play a critical role in skin carcinogenesis. A malignant skin keratinocyte cell line (308), which carries a H-ras mutation at codon 61, showed elevated p53 levels, increased caspase 3 activity and enhanced apoptosis after TPA treatment. In contrast, the non-malignant counterpart (C50) showed undetectable levels of p53 and less apoptosis than 308 cells similarly treated. Inhibition of NADPH-oxidase (NOX) by diphenyleneiodonium suppressed p53 activation and apoptosis in 308 cells, linking Ras mutation to NOX-induced p53 activation, which was further supported by the finding that siRNA to Rac1 inhibited p53 activation after TPA treatment. Application of DPI to DMBA-initiated skin tissue significantly blocked TPA-mediated increased p53 levels and reduced apoptosis in skin epidermal tissues. Taken together, our results suggest that NOX bridges oncogenic activation and p53 mitochondrial translocation to apoptosis in the multistage chemical-induced skin carcinogenesis model.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Cancer Res.Home page
G. Wei, K. DeFeo, C. S. Hayes, P. M. Woster, L. Mandik-Nayak, and S. K. Gilmour
Elevated Ornithine Decarboxylase Levels Activate Ataxia Telangiectasia Mutated-DNA Damage Signaling in Normal Keratinocytes
Cancer Res., April 1, 2008; 68(7): 2214 - 2222.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.