Abrogation of protein phosphatase 6 promotes skin carcinogenesis induced by DMBA
| Autor: | Yoichiro Kakugawa, Masami Suganuma, Hiroshi Kiyonari, Hiroshi Shima, Mai Suzuki, Shigemi Ito, Nobuhiro Tanuma, Kayoko Fukamachi, Miyuki Nomura, M Sakayori, Akira Suzuki, Yoji Yamashita, Ayako Kishimoto, Honami Ogoh, Miki Nishio, Yuki Momoi, Y Sakamoto, Hiroyuki Kato, Y Inoue, Toshio Watanabe, Katsuhisa Hayashi, Ikuro Sato |
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| Rok vydání: | 2014 |
| Předmět: |
Keratinocytes
Cancer Research Skin Neoplasms Carcinogenesis 9 10-Dimethyl-1 2-benzanthracene Phosphatase DMBA Mice Transgenic Biology medicine.disease_cause Conditional gene knockout Genetics medicine Phosphoprotein Phosphatases Animals Molecular Biology Cells Cultured Skin Melanoma NF-kappa B Interleukin medicine.disease NFKB1 Mice Inbred C57BL Cancer research Mice Inbred CBA Tumor necrosis factor alpha Signal Transduction |
| Zdroj: | Oncogene. 34(35) |
| ISSN: | 1476-5594 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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