Ppp6c-deficiency and cancer predisposition

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K20237
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Miyagi Prefectural Hospital Organization Miyagi Cancer Center
• Principal Investigator: MOMOI Yuki 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 共同研究員 (10750440)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 口腔咽頭科学

Outline of Final Research Achievements

Several experiment using biochemical experiments have suggested that protein phosphatase 6 (PP6) functions at cell cycle check point, suppresses NFkB signaling, and also functions in DNA repair. However, whether PP6 is involved in carcinogenesis has not been examined. We previously reported that deficiency in the gene encoding the catalytic subunit of protein phosphatase 6 (Ppp6c) predisposes mouse skin tissue to papilloma formation initiated by DMBA. Then, we demonstrated that Ppp6c loss acts as a tumor promoter in UVB-induced basal cell carcinogenesis. Importantly, somatic mutations in Ppp6c gene have been identified in approximately 10% of malignant melanoma patients harboring Braf or Nras mutations. In this experiment, we found that induction of double mutation (Ppp6c deficiency and KrasG12D expression) in the cytokeratin 14 positive cells drives cell proliferation, and leaded to hyperplasia of squamous epithelium tissue.

Free Research Field

医歯薬学