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

Research Project

Project/Area Number 15K10081
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General surgery
Research InstitutionMiyagi 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
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords紫外線発がん / プロテインホスファターゼ / 実験外科学
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.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (21 results)

All 2018 2017 2016 2015

All Journal Article (13 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 13 results,  Open Access: 8 results,  Acknowledgement Compliant: 3 results) Presentation (8 results)

  • [Journal Article] Loss of protein phosphatase 6 in mouse keratinocytes enhances K-rasG12D-driven tumor promotion.2018

    • Author(s)
      Kurosawa K, Inoue Y, Kakugawa Y, Yamashita Y, Kanazawa K, Kishimoto K, Nomura M, Momoi Y, Sato I, Chiba N, Suzuki M, Ogoh H, Yamada H, Miura K, Watanabe T, Tanuma N, Tachi M, and Shima H
    • Journal Title

      Cancer Science

      Volume: 印刷中

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Associations of cigarette smoking and alcohol drinking with stomach cancer survival: A prospective patient cohort study in Japan2018

    • Author(s)
      Minami Yuko、Kanemura Seiki、Oikawa Tomoyuki、Suzuki Shinichi、Hasegawa Yasuhiro、Miura Koh、Nishino Yoshikazu、Kakugawa Yoichiro、Fujiya Tsuneaki
    • Journal Title

      International Journal of Cancer

      Volume: - Issue: 5 Pages: 1072-1085

    • DOI

      10.1002/ijc.31408

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular and clinical features of the TP53 signature gene expression profile in early-stage breast cancer.2018

    • Author(s)
      Yamaguchi S, Takahashi S, Mogushi K, Izumi Y, Nozaki Y, Nomizu T, Kakugawa Y, Ishida T, Ohuchi N, Ishioka C, Kato S.
    • Journal Title

      Oncotarget

      Volume: 9(18) Issue: 18 Pages: 14193-14206

    • DOI

      10.18632/oncotarget.24447

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantitative diagnostic imaging of cancer tissues by using phosphor-integrated dots with ultra-high brightness.2017

    • Author(s)
      Gonda Kohsuke
    • Journal Title

      scientific reports

      Volume: - Issue: 1 Pages: 7509-7509

    • DOI

      10.1038/s41598-017-06534-z

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Drug delivery of oral anti-cancer fluoropyrimidine agents.2017

    • Author(s)
      Miura K, Shima H, Takebe N, Julie R, Satoh K, Kakugawa Y, Satoh M, Kinouchi M, Yamamoto K, Hasegawa Y, Kawai M, Kanazawa K, Fujiya T, Unno M and Katakura R.
    • Journal Title

      Expert Opin.Drug Deliv

      Volume: 印刷中 Issue: 12 Pages: 1-12

    • DOI

      10.1080/17425247.2017.1316260

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Associations of obesity and physical activity with serum and intratumoral sex steroid hormone levels among postmenopausal women with breast cancer: analysis of paired serum and tumor tissue samples.2017

    • Author(s)
      Yoichiro Kakugawa, Hiroshi Tada, Masaaki Kawai, Takashi Suzuki, Yoshikazu Nishino, Seiki Kanemura, Takanori Ishida, Noriaki Ohuchi, Yuko Minami
    • Journal Title

      Breast Cancer Res Treat

      Volume: 162(1) Issue: 1 Pages: 115-125

    • DOI

      10.1007/s10549-016-4094-3

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Minimal impact of postmastectomy radiation therapy on locoregional recurrence for breast cancer patients with 1 to 3 positive lymph nodes in the modern treatment era2017

    • Author(s)
      Minoru Miyashita, Hiroshi Tada, Akihiko Suzuki, Gou Watanabe, Hisashi Hirakawa, Masakazu Amari, Yoichiro Kakugawa, Masaaki Kawai, Akihiko Furuta, Kaoru Sato, Ryuichi Yoshida, Akiko Ebata, Hironobu Sasano, Keiichi Jingu, Noriaki Ohuchi, Takanori Ishida
    • Journal Title

      Surgical Oncology

      Volume: 26(2) Issue: 2 Pages: 163-170

    • DOI

      10.1016/j.suronc.2017.03.003

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Abrogation of protein phosphatase 6 promotes skin carcinogenesis induced by DMBA2015

    • 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

    • Related Report
      2015 Research-status Report
    • 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

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Smoking and survival after breast cancer diagnosis in Japanese women: A prospective cohort study.2015

    • Author(s)
      Yoichiro Kakugawa, Masaaki Kawai, Yoshikazu Nishino, Kayoko Fukamachi,Takanori Ishida,Noriaki Ohuchi and Yuko Minami
    • Journal Title

      Cancer Sci

      Volume: 106 Issue: 8 Pages: 1066-1074

    • DOI

      10.1111/cas.12716

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Personality and breast cancer risk and survival: the Miyagi Cohort Study2015

    • Author(s)
      Yuko Minami, Toru Hosokawa, Naoki Nakaya, Yumi Sugawara, Yoshikazu Nishino, Yoichiro Kakugawa, Akira Fukao, Ichiro Tsuji
    • Journal Title

      Breast Cancer Research and Treatment

      Volume: 150 Issue: 3 Pages: 675-684

    • DOI

      10.1007/s10549-015-3364-9

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The use of natural products in colorectal cancer drug discovery.2015

    • Author(s)
      Koh Miura, Masayuki Satoh, Makoto Kinouchi, Kuniharu Yamamoto, Yasuhiro Hasegawa, Yoichiro Kakugawa, Masaaki Kawai, Kiyoshi Uchimi, Hiroki Aizawa, Shinobu Ohnuma, Taiki Kajiwara, Hiroto Sakurai , Tsuneaki Fujiya
    • Journal Title

      Expert opinion on drug discovery

      Volume: 10(4) Issue: 4 Pages: 411-426

    • DOI

      10.1517/17460441.2015.1018174

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Immunolocalization of thymidylate synthase as a favorable prognostic marker in estrogen receptor-positive breast carcinoma.2015

    • Author(s)
      Kiyoshi Takagi, Yasuhiro Miki, Yasuhiro Nakamura, Hisashi Hirakawa, Yoichiro Kakugawa, Goro Amano, Mika Watanabe, Takanori Ishida, Hironobu Sasano and Takashi Suzuki
    • Journal Title

      Histology and histopathology

      Volume: 30 Pages: 1223-1232

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] Ppp6c は、マウス皮膚のがん抑制遺伝子として働く2017

    • Author(s)
      黒沢是之、野村美有樹、角川陽一郎、山下洋二、三浦康、山田秀和、松浦一登、佐藤郁郎、田沼延公、渡邊利雄、島礼
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 新規皮膚がん抑制遺伝子Ppp6c変異は、変異型K-RASによる腫瘍発生を強く促進する2016

    • Author(s)
      黒沢是之、田沼延公、角川陽一郎、山下洋二、三浦康、山田秀和、佐藤郁郎、野村美有樹、渡利雄、島礼
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      神奈川県・横浜市
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] パーソナリティーと乳がん罹患・死亡リスクとの関連2016

    • Author(s)
      角川 陽一郎、西野 善一、吉田 薫、辻 一郎、南 優子
    • Organizer
      第24回 日本乳癌学会学術総会
    • Place of Presentation
      東京
    • Year and Date
      2016-06-17
    • Related Report
      2016 Research-status Report
  • [Presentation] 自己記入式質問紙調査による遺伝性乳がん卵巣がん症候群の拾い上げの現状と課題2016

    • Author(s)
      河合 賢朗、角川 陽一郎、五安城 芙由子、安田 有理、佐藤 馨、 古田 昭彦
    • Organizer
      第24回 日本乳癌学会学術総会
    • Place of Presentation
      東京
    • Year and Date
      2016-06-17
    • Related Report
      2016 Research-status Report
  • [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
    • Related Report
      2015 Research-status Report
  • [Presentation] 大腸癌における天然物を用いた抗がん剤開発の現況2015

    • Author(s)
      三浦康、島礼、佐藤賢一、山口壹範、田沼延公、角川陽一郎、佐藤正幸、木内誠、山本久仁治、長谷川康弘、河合賢朗、大沼忍、藤谷恒明
    • 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
    • Related Report
      2015 Research-status Report
  • [Presentation] Alcohol intake and breast cancer risk according to joint estrogen and progesterone receptor status:a case-control study.2015

    • Author(s)
      Yoko Takizawa, Masaaki Kawai, Yoshikazu Nishino, Yoichiro Kakugawa, Yuko Minami
    • 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
    • Related Report
      2015 Research-status Report
  • [Presentation] 乳癌組織中ホルモン濃度と肥満度、運動習慣、飲酒との関連。2015

    • Author(s)
      角川陽一郎、河合賢朗、西野善一、南優子
    • Organizer
      第23回 日本乳癌学会総会
    • Place of Presentation
      東京国際フォーラム(千代田区・東京都)
    • Year and Date
      2015-07-02
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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