Involvement of DNA repair protein REV7 in cell proliferation, mobility and organogenesis

• Project/Area Number: 19590387
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Nagoya University
• Principal Investigator: MURAKUMO Yoshiki Nagoya University, 大学院・医学系・研究科, 准教授 (40324438)
• Co-Investigator(Kenkyū-buntansha): JIJIWA Mayumi 名古屋大学, 大学院・医学系研究科, COE特任講師 (50378006)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: REV7 / DNA修復 / 細胞周期調節 / ノックアウトマウス / 結合蛋白 / マススペクロトメトリー / マススペクトロメトリー / 相同組み換え体 / REV7結合蛋白

Research Abstract

REV7の個体発生における重要性を検討するために、REV7ノックアウトマウスの樹立を行った。ノックアウトベクターの作成、相同組み換えES細胞の同定、キメラマウスの作成を経て、REV7ヘテロノックアウトマウスまで確立した。ヘテロノックアウトマウスは外見上wild typeマウスと変わり無く、成長も正常で生殖能力もあることまで判明した。また、REV7の細胞レベルでの重要性を検討するために、マススペクロトメトリーを利用してREV7結合蛋白の同定を行い、DNA修復、発癌、遺伝子発現、シグナル伝達に関与する蛋白が複数同定された。

Research Products

• [Journal Article] Upregulation of CD109 expression is associated with carcinogenesis of the squamous epithelium of the oral cavity (2008)
  • Author(s): Hagiwara S, Murakumo Y, Sato T, Shigetomi T, Mitsudo K, Tohnai I, Ueda M Takahashi M.
  • Journal Title: Cancer Sci 99 Pages: 1916-23
  • NAID: 10024011720
  • Peer Reviewed
• [Journal Article] RETチロシンキナーゼの生理機能 (2008)
  • Author(s): 村雲芳樹, 高橋雅英
  • Journal Title: 細胞 40巻14号、 Pages: 600-603
• [Journal Article] Roles of induced expression of MAPK phosphatase-2 in tumor development in RET-MEN2A transgenic mice (2008)
  • Author(s): Hasegawa T, Enomoto A, Kato T, Kawai K, Miyamoto R, Jijiwa M, Ichihara M, Ishida M, Asai N, Murakumo Y, Ohara K, Niwa Y, Goto H, Takahashi M.
  • Journal Title: Oncogene 27 Pages: 5684-95
  • Peer Reviewed
• [Journal Article] CD109 expression in basal-like breast carcinoma (2008)
  • Author(s): Hasegawa M, Moritani S, Murakumo Y, Sato T, Hagiwara S, Suzuki C, Mii S, Jijiwa M, Enomoto A, Asai N, Ichihara S, Takahashi M.
  • Journal Title: Pathol Int 58 Pages: 288-94
  • NAID: 10027376587
  • Peer Reviewed
• [Journal Article] GDNF-mediated signaling via RET tyrosine 1062 is essential for maintenance of spermatogonial stem cells (2008)
  • Author(s): Jijiwa M, Kawai K, Fukihara J, Nakamura A, Hasegawa M, Suzuki C, Sato T, Enomoto A, Asai N, Murakumo Y, Takahashi M
  • Journal Title: Genes Cells 13 Pages: 365-74
  • Peer Reviewed
• [Journal Article] An actin-binding protein Girdin regulates the motility of breast cancer cells (2008)
  • Author(s): Jiang P, Enomoto A, Jijiwa M, Kato T, Hasegawa T, Ishida M, Sato T, Asai N, Murakumo Y, Takahashi M.
  • Journal Title: Cancer Res 68 Pages: 1310-8
  • Peer Reviewed
• [Journal Article] A novel GDNF-inducible gene, BMZF3, encodes a transcriptional repressor associated with KAP-1 (2008)
  • Author(s): Suzuki C, Murakumo Y, Kawase Y, Sato T, Morinaga T, Fukuda N, Enomoto A, Ichihara M, Takahashi M.
  • Journal Title: Biochem Biophys Res Commun 366 Pages: 226-32
  • Peer Reviewed
• [Journal Article] Thermodynamic instability of siRNA duplex is a prerequisite for dependable prediction of siRNA activites (2008)
  • Author(s): Ichihara M, Murakumo Y, Masuda A, Matsuura T, Asai N, Jijiwa M, Ishida M, Shinmi J, Yatsuya H, Qiao S, Takahashi M, Ohno K
  • Journal Title: Nucleic Acids Res 35
  • Peer Reviewed
• [Journal Article] CD109病理診断とがん研究への応用 (2008)
  • Author(s): 村雲芳樹, 高橋雅英
  • Journal Title: 病理と臨床 25-10 Pages: 1058-1059
• [Journal Article] A novel GDNF-inducible gene, BMZF3, encodes a transcriptional repressor associated with KAP-1. (2008)
  • Author(s): Suzuki C
  • Journal Title: Biochem Biophys Res Commun 366 Pages: 226-232
  • Peer Reviewed
• [Journal Article] An actin-binding protein Girdin regulates the motility of breast cancer cells. (2008)
  • Author(s): Jiang P
  • Journal Title: Cancer Res 68 Pages: 1310-1318
  • Peer Reviewed
• [Journal Article] GDNF-mediated signaling via RET tyrosine 1062 is essential for maintenance of spermatogonial stem cells. (2008)
  • Author(s): Jijiwa M
  • Journal Title: Genes Cells 13 Pages: 365-374
  • Peer Reviewed
• [Journal Article] CD109 expression in basal-like breast carcinoma. (2008)
  • Author(s): Hasegawa M
  • Journal Title: Pathol Int 58 Pages: 288-294
  • Peer Reviewed
• [Journal Article] Roles of induced expression of MAPK phosphatase-2 in tumor development in RET-MEN2A transgenic mice. (2008)
  • Author(s): Hasegawa T
  • Journal Title: Oncogene 27 Pages: 5684-5695
  • Peer Reviewed
• [Journal Article] Upregulation of CD 109 expression is associated with carcinogenesis of the squamous epithelium of the oral cavity. (2008)
  • Author(s): Hagiwara S
  • Journal Title: Cancer Sci 99 Pages: 1916-1923
  • Peer Reviewed
• [Journal Article] A novel GDNF-inducible gene, BMZF3, encodes a transcriptional repress or associated with KAP-1. (2008)
  • Author(s): Suzuki C
  • Journal Title: Biochem Biophys Res Commun. 366 Pages: 226-232
  • Peer Reviewed
• [Journal Article] Nucleolin modulates the subcellular localization of GDNF inducible zinc finger protein 1 and its roles in transcription and cell proliferation (2007)
  • Author(s): Dambara A, Morinaga T, Fukuda N, Yamakawa Y, Kato T, Enomoto A, Asai N, Murakumo Y, Matsuo S, Takahashi M.
  • Journal Title: Exp Cell Res 313 Pages: 3755-66
  • Peer Reviewed
• [Journal Article] High-level expression of CD109 is frequently detected in lung squamous cell carcinomas (2007)
  • Author(s): Sato T, Murakumo Y, Hagiwara S, Jijiwa M, Suzuki C, Yatabe Y, Takahashi M.
  • Journal Title: Pathol Int 57 Pages: 719-24
  • NAID: 10021234139
  • Peer Reviewed
• [Journal Article] Rad9 modulates the P21WAF1 pathway by direct association with p53 (2007)
  • Author(s): Ishikawa K, Ishii H, Murakumo Y, Mimori K, Kobayashi M, Yamamoto K, Mori M, Nishino H, Furukawa Y, Ichimura K.
  • Journal Title: BMC Mol Biol 8 Pages: 37-37
  • NAID: 120001138323
  • Peer Reviewed
• [Journal Article] Sprouty2 regulates growth and differentiation of human neuroblastoma cells through RET tyrosine kinase (2007)
  • Author(s): Ishida M, Ichihara M, Mii S, Jijiwa M, Asai N, Enomoto A, Kato T, Majima A, Ping J, Murakumo Y, Takahashi M
  • Journal Title: Cancer Sci 98 Pages: 815-21
  • Peer Reviewed
• [Journal Article] CD109, a new marker for myoepithelial cells of mammary, salivary, and lacrimal glands and prostate basal cells (2007)
  • Author(s): Hasegawa M, Hagiwara S, Sato T, Murakumo Y, Maeda M, Moritani S, Ichihara S, Takahashi M.
  • Journal Title: Pathol Int 57 Pages: 245-50
  • NAID: 10020104230
  • Peer Reviewed
• [Journal Article] High-level expression of CD109 is frequently detected in lung squamous cell car cinomas. (2007)
  • Author(s): Sato T
  • Journal Title: Pathol Int, 57 Pages: 719-724
  • Peer Reviewed
• [Journal Article] Nucleolin modulates the subcellular localization of GDNF-inducible zinc finger protein 1 and its roles in transcription and cell proliferation. (2007)
  • Author(s): Dambara A
  • Journal Title: Exp Cell Res 313 Pages: 3755-3766
  • Peer Reviewed
• [Presentation] ヒトREV7及びMAD2タンパク質の結合モチーフ配列の部分的オーバーラッピング (2008)
  • Author(s): 花房朋, 村雲芳樹, 土生敏行, 原幸大, 橋本博, 大橋英治, 大森治夫
  • Organizer: 第31回日本分子生物学会
  • Place of Presentation: 神戸
• [Presentation] 皮膚腫瘍におけるCD109の発現(CD109 expression in skin tumor) (2008)
  • Author(s): 長谷川正規, 森谷鈴子, 村雲芳樹, 市原周, 高橋雅英
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] 遺伝性の癌その研究と臨床の最前線RETチロシンキナーゼのシグナル伝達と発がん(Forefront of Basic and Clinical Researches in Hereditary Cancer Role of RET tyrosine kinase signaling in tumor development) (2008)
  • Author(s): 高橋雅英, 長谷川太作, 榎本篤, 加藤琢哉, 石田麻紀, 時々輪真由美, 浅井直也, 村雲芳樹, 後藤秀実
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] TBP-2の発現抑制に関わる転写複合体の解析(Characterization of the transcription complex involved in the TBP-2 repression) (2008)
  • Author(s): 加藤琢哉, 下野洋平, 榎本篤, 時々輪真由美, 村雲芳樹, 高橋雅英
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] 口腔癌におけるCD109の発現(CD109 expression in oral cancer) (2008)
  • Author(s): 萩原純孝, 村雲芳樹, 重冨俊雄, 光藤健司, 藤内祝, 上田実, 高橋雅英
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] 基底細胞型乳癌の新しいマーカーとしてのCD109 (2008)
  • Author(s): 長谷川正規, 森谷鈴子, 三井伸二, 佐藤朋子, 時々輪真由美, 村雲芳樹, 市原周, 高橋雅英
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢
• [Presentation] 乳腺腺筋上皮腫(adenomyoepithelioma)の1例 (2008)
  • Author(s): 時々輪真由美, 市原周, 長谷川正規, 佐藤朋子, 鈴木智景, 三井伸二, 榎本篤, 森谷鈴子, 浅井直也, 村雲芳樹, 高橋雅英
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢
• [Presentation] Choroid plexus papillary carcinomaの一例 (2008)
  • Author(s): 鈴木智景, 岩田洋介, 村雲芳樹, 榎本篤, 三井伸二, 下山芳江, 長坂徹郎, 高橋雅英
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢
• [Presentation] High-level expression of CD109 is frequently detected in lung squamous cell carcinomas (2008)
  • Author(s): Murakumo Y, Sato T, Hashimoto M, Zhang J, Takahashi M.
  • Organizer: 99th Annual Meeting, American association for Cancer Research
  • Place of Presentation: San Diego, USA
• [Presentation] High-level expression of CD109 is frequently detected in lung squamous cell carcinomas. (2008)
  • Author(s): Murakumo, Y
  • Organizer: 99th Annual Meeting, American association for Cancer Research
  • Place of Presentation: San Diego, USA
• [Presentation] 基底細胞型乳癌の新しいマーカーとしてのCD109. (2008)
  • Author(s): 長谷川正規
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢
• [Presentation] 乳腺腺筋上皮腫(adenomyoepithelioma)の1例. (2008)
  • Author(s): 時々輪真由美
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢
• [Presentation] Choroid plexus papillary carcinomaの一例. (2008)
  • Author(s): 鈴木智景
  • Organizer: 第97回日本病理学会総会
  • Place of Presentation: 金沢
• [Presentation] 皮膚腫瘍におけるCD109の発現 (2008)
  • Author(s): 長谷川正規
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] 遺伝性の癌 その研究と臨床の最前線 RETチロシンキナーゼのシグナル伝達と発がん (2008)
  • Author(s): 高橋雅英
  • Organizer: 第67回目本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] TBP-2の発現抑制に関わる転写複合体の解析 (2008)
  • Author(s): 加藤琢哉
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] 口腔癌におけるCD109の発現(CD109 expression in oral cancer). (2008)
  • Author(s): 萩原純孝
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] 基底細胞型乳癌の新規マーカーとしてのCD109 (2007)
  • Author(s): 長谷川正規, 森谷鈴子, 佐藤朋子, 時々輪真由美, 村雲芳樹, 市原周, 高橋雅英
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] Sprouty2はRETチロシンキナーゼ下流シグナルによる神経芽細胞種の増殖と分化を調節する (2007)
  • Author(s): 石田麻紀, 市原正智, 三井伸二, 時々輪真由美, 浅井直也, 榎本篤, 加藤琢哉, 村雲芳樹, 高橋雅英
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] MAPKホスファターゼ-2(MKP2)はMEN2Aトランスジェニックマウス由来の乳癌細胞の増殖とアポトーシスを制御する (2007)
  • Author(s): 長谷川太作, 榎本篤, 川井久美, 加藤琢哉, 時々輪真由美, 浅井直也, 村雲芳樹, 後藤秀実, 高橋雅英
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] 肺扁平上皮癌におけるCD109の発現 (2007)
  • Author(s): 佐藤朋子, 村雲芳樹, 萩原純孝, 時々輪真由美, 矢田部恭, 高橋雅英
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] 神経栄養因子GDNFによって発現誘導される遺伝子BMZF-3の機能解析 (2007)
  • Author(s): 鈴木智景, 村雲芳樹, 市原正智, 高橋雅英
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] 転写制御因子RFPによる細胞増殖制御 (2007)
  • Author(s): 加藤琢哉, 時々輪真由美, 川井久美, 村雲芳樹, 高橋雅英
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
• [Presentation] hREV7とクラスリン軽鎖間の相互作用の解析 (2007)
  • Author(s): 村雲芳樹, 高橋雅英
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
• [Book] 病理と臨床 (2007)
  • Author(s): 村雲芳樹
  • Total Pages: 116
  • Publisher: 文光堂