PP6 as a tumor suppressor in mouse two-stage chemical carcinogenesis

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10081
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Miyagi Prefectural Hospital Organization Miyagi Cancer Center
• Principal Investigator: KAKUGAWA Yoichiro 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, 特任研究員 (60221173)
• Co-Investigator(Kenkyū-buntansha): 島 礼 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, 部長 (10196462) ; 佐藤 郁郎 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), ティッシュバンクセンター, 部長 (50225918)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 紫外線発がん / プロテインホスファターゼ

Outline of Final Research Achievements

Recently, to determine whether PP6 deficiency functions in carcinogenesis in vivo, we employed a mouse skin 2-stage carcinogenesis model. We found that a single DMBA application was sufficient to produce papillomas in Ppp6c-deficient skin. As such, ours was the first report that Ppp6c loss-of-function acts as a tumor promoter in mice. Here, we investigated effect of UVB radiation on mouse keratinocytes in which Ppp6c had been deleted. Following UVB irradiation, mice with Ppp6c-deficient keratinocytes showed a higher incidence of skin squamous cell carcinoma than did control mice. We concluded that Ppp6c loss-of-function in mouse skin showed hypersensitivity to UVB-induced squamous cell carcinoma. Our histochemical analyses suggest that Ppp6c deficiency underlies molecular events that drive outgrowth of initiated keratinocytes harboring UVB-induced mutated p53.

Free Research Field

医歯薬学