| Literature DB >> 25486434 |
K Hayashi1,2, Y Momoi1, N Tanuma1,2, A Kishimoto3, H Ogoh3, H Kato1,2, M Suzuki3, Y Sakamoto1, Y Inoue1, M Nomura1, H Kiyonari4, M Sakayori1, K Fukamachi1, Y Kakugawa1, Y Yamashita1, S Ito5, I Sato5, A Suzuki6, M Nishio6, M Suganuma7, T Watanabe3, H Shima1,2.
Abstract
Somatic mutations in the gene encoding the catalytic subunit of protein phosphatase 6 (Ppp6c) have been identified in malignant melanoma and are thought to function as a driver in B-raf- or N-ras-driven tumorigenesis. To assess the role of Ppp6c in carcinogenesis, we generated skin keratinocyte-specific Ppp6c conditional knockout mice and performed two-stage skin carcinogenesis analysis. Ppp6c deficiency induced papilloma formation with 7,12-dimethylbenz (a) anthracene (DMBA) only, and development of those papillomas was significantly accelerated compared with that seen following DMBA/TPA (12-O-tetradecanoylphorbol 13-acetate) treatment of wild-type mice. NF-κB activation either by tumor necrosis factor (TNF)-α or interleukin (IL)-1β was enhanced in Ppp6c-deficient keratinocytes. Overall, we conclude that Ppp6c deficiency predisposes mice to skin carcinogenesis initiated by DMBA. This is the first report showing that such deficiency promotes tumor formation in mice.Entities:
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Year: 2014 PMID： 25486434 DOI： 10.1038/onc.2014.398
Source DB: PubMed Journal: Oncogene ISSN： 0950-9232 Impact factor: 9.867