Abrogation of protein phosphatase 6 promotes skin carcinogenesis induced by DMBA

作者：Hayashi K; Momoi Y; Tanuma N; Kishimoto A; Ogoh H; Kato H; Suzuki M; Sakamoto Y; Inoue Y; Nomura M; Kiyonari H; Sakayori M; Fukamachi K; Kakugawa Y; Yamashita Y; Ito S; Sato I; Suzuki A; Nishio M; Suganuma M; Watanabe T; Shima H^*

来源：Oncogene, 2015, 34(35): 4647-4655.

DOI：10.1038/onc.2014.398

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-kappa B activation either by tumor necrosis factor (TNF)-alpha or interleukin (IL)-1 beta 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.

• 出版日期2015-8-27
• 单位RIKEN