Function of Ppp6c as a tumor suppressor gene

• Project/Area Number: 15K19081
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Miyagi Prefectural Hospital Organization Miyagi Cancer Center
• Principal Investigator: HAYASHI Katuhisa 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 (30726302)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 腫瘍

Outline of Final Research Achievements

Using a 2-stage skin carcinogenesis model, we found that a single DMBA application was sufficient to produce papillomas in Protein phosphatase 6 catalytic subunit (Ppp6c)-deficient skin. The data suggests that Ppp6c-deficient skin is predisposed to carcinogenesis initiated by DMBA. Ppp6c-deficient skin tissues show an enhanced inflammatory response following DMBA treatment. Ppp6c-deficient tissue samples exhibited thicker epidermis associated with hyperkeratosis, cellular infiltration of the dermis, and disappearance of subcutaneous fat tissue, indicating inflammatory and proliferative responses. Expression of inflammation-related genes is upregulated by DMBA treatment and that this effect that is more significant in Ppp6c-deficient skin. Molecular mechanism underlying its pathogenesis is thought to be that TNF-α- and IL-1β-dependent NF-kB signaling is enhanced in Ppp6c-deficient keratinocytes.

Research Products

• [Journal Article] Abrogation of protein phosphatase 6 promotes skin carcinogenesis induced by DMBA (2015)
  • Author(s): 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, and Shima H
  • Journal Title: Oncogene Volume: 印刷中 Issue: 35 Pages: 4647-55
  • DOI: 10.1038/onc.2014.398
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Loss of protein phosphatase 6 in mouse keratinocytes increases susceptibility to ultraviolet-B-induced carcinogenesis. (2015)
  • Author(s): Kato H, Kurosawa K, Inoue Y, Tanuma N, Momoi Y, Hayashi K, Ogoh H, Nomura M, Sakayori M, Kakugawa Y, Yamashita Y, Miura K, Maemondo M, Katakura R, Ito S, Sato M, Sato I, Chiba N, Watanabe T, Shima H.
  • Journal Title: Cancer Lett. Volume: 365 Issue: 2 Pages: 223-228
  • DOI: 10.1016/j.canlet.2015.05.022
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Beclomethasone dipropionate腸溶性カプセルの調製と品質の検討 (2016)
  • Author(s): 内田敬、鈴木裕之、林克剛、楢岡美香、猪岡京子、八木朋美、岸川幸生、我妻恭行、
  • Organizer: 第26回医療薬学会年会
  • Place of Presentation: 京都
  • Year and Date: 2016-09-17
• [Presentation] "プロテインホスファターゼ6型(PP6)は、皮膚がん抑制遺伝子として働く (2016)
  • Author(s): 井上 維、黒沢 是之、小河 穂波、加藤 浩之、林 克剛、野村 美有樹、田沼 延公、渡邊 利雄、島 礼
  • Organizer: 平成27年度 個体レベルでのがん研究支援活動 ワークショップ
  • Place of Presentation: 琵琶湖ホテル（滋賀県・大津市）
  • Year and Date: 2016-02-03
• [Presentation] 皮膚Ppp6c欠損マウスは、UVB誘導皮膚扁平上皮発がんに高感受性となる (2015)
  • Author(s): 加藤浩之、田沼延公、三浦康、角川陽一郎、椎葉健一、山下洋二、林克剛、野村美有樹、佐藤郁郎、伊藤しげみ、渡邊利雄、島礼
  • Organizer: 第74回 日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知県・名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] UVB照射により、Ppp6c欠損では、高頻度に皮膚扁平上皮癌が発生する (2015)
  • Author(s): 加藤浩之、田沼延公、黒沢是之、井上維、林克剛、小河穂波、野村美有樹、渡邊利雄,島礼
  • Organizer: 第81回 日本化学会東北支部例会
  • Place of Presentation: 東北大学さくらホール（宮城県・仙台市）
  • Year and Date: 2015-05-09