Tumor promotion associated with Ppp6c-deficiency.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26430130
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Miyagi Prefectural Hospital Organization Miyagi Cancer Center
• Principal Investigator: SHIMA Hiroshi 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)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: プロテインホスファターゼ / 炎症 / DNA修復 / ゲノム不安定性 / ドライバー変異

Outline of Final Research Achievements

We showed that a single DMBA application was sufficient to produce papillomas in Ppp6c-deficient skin and tumor promotion associated with Ppp6c-deficiency is more significant than that seen after repeated applications of TPA. as such, ours was the first report that Ppp6c loss-of-function acts as a tumor promoter in mice. However, it remained unclear whether (1) tumor promotion is specific to DMBA as an initiator or (2) is limited to papilloma or carcinoma formation. To answer these questions, we performed UVB induced carcinogenesis experiment. Following UVB irradiation, mice with Ppp6c-deficient keratinocytes showed a higher incidence of skin basal cell carcinoma than did control mice. UVB-induced tumors in Ppp6c-deficient keratinocytes exhibited a high frequency of both p53- andγH2AX-positive cells, suggestive of DNA damage. Epidemiological and molecular data strongly suggest that Ppp6c is one of the suppressor gene for UVB-induced human skin cancers.

Free Research Field

総合生物