title: Abrogation of protein phosphatase 6 promotes skin carcinogenesis induced by DMBA.
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.
authors.affiliation: Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Miyagi, Japan.|Division of Cancer Molecular Biology, Tohoku University School of Medicine, Miyagi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Miyagi, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Momoi
authors.affiliation: Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Miyagi, Japan.|Division of Cancer Molecular Biology, Tohoku University School of Medicine, Miyagi, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Tanuma
authors.affiliation: Department of Biological Science, Graduate School of Humanities and Sciences, Nara Women's University, Nara, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kishimoto
authors.affiliation: Department of Biological Science, Graduate School of Humanities and Sciences, Nara Women's University, Nara, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ogoh
authors.affiliation: Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Miyagi, Japan.|Division of Cancer Molecular Biology, Tohoku University School of Medicine, Miyagi, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.affiliation: Department of Biological Science, Graduate School of Humanities and Sciences, Nara Women's University, Nara, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Miyagi, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sakamoto
authors.affiliation: Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Miyagi, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Miyagi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nomura
authors.affiliation: Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, Kobe, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kiyonari
authors.affiliation: Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Miyagi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Sakayori
authors.affiliation: Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Miyagi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Fukamachi
authors.affiliation: Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Miyagi, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kakugawa
authors.affiliation: Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Miyagi, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yamashita
authors.affiliation: Division of Pathology, Miyagi Cancer Center, Miyagi, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ito
authors.affiliation: Division of Pathology, Miyagi Cancer Center, Miyagi, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Sato
authors.affiliation: Division of Cancer Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Suzuki
authors.affiliation: Division of Cancer Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nishio
authors.affiliation: Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Suganuma
authors.affiliation: Department of Biological Science, Graduate School of Humanities and Sciences, Nara Women's University, Nara, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Miyagi, Japan.|Division of Cancer Molecular Biology, Tohoku University School of Medicine, Miyagi, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Shima
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism; D002478:Cells, Cultured; D015603:Keratinocytes / Q000201:enzymology; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin / Q000201:enzymology / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000201:enzymology*
chemical_list: D016328:NF-kappa B; D015127:9,10-Dimethyl-1,2-benzanthracene; D010749:Phosphoprotein Phosphatases; C106079:protein phosphatase 6