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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/23003
Title: Ras mutation promotes p53 activation and apoptosis of skin keratinocytes
Authors: Yunfeng Zhao
Luksana Chaiswing
Vasudevan Bakthavatchalu
Terry D. Oberley
Daret K. St. Clair
University of Kentucky College of Medicine
University of Wisconsin Madison
Mahidol University
Louisiana State University in Shreveport
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Aug-2006
Citation: Carcinogenesis. Vol.27, No.8 (2006), 1692-1698
Abstract: 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. © 2006 Oxford University Press.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=33747885052&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/23003
ISSN: 14602180
01433334
Appears in Collections:Scopus 2006-2010

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