Significance of REV7 for germ cell maintenance and spermatogenesis

• Project/Area Number: 24590479
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Kitasato University
• Principal Investigator: MURAKUMO Yoshiki 北里大学, 医学部, 教授 (40324438)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: REV7 / 精子形成 / DNA損傷 / コンディショナルノックアウトマウス / トランスジェニックマウス / 精巣 / Rev7 / 生殖細胞 / DNA修復 / ノックアウトマウス / Spermatogenesis

Outline of Final Research Achievements

To make clear roles of REV7 in spermatogenesis in the testis, we tried to generate Rev7 conditional knockout mouse, in which Rev7 could be deleted in the adult period. Because we could not generate the mouse in our first plan, we purchased commercially-available gene targeted mouse and are now generating the Rev7 conditional knockout mouse. We performed another project to identify REV7-interacting proteins in the testis using Rev7 transgenic mouse testes. Although several candidate bands were detected in the immunoprecipitation analysis, we could not analyze them by mass spectrometry because of less amount of the proteins. We will continue the project in the future.

Research Products

• [Journal Article] Suppression of REV7 enhances cisplatin sensitivity in ovarian clear cell carcinoma cells. (2014)
  • Author(s): Niimi K, Murakumo Y, Watanabe N, Kato T, Mii S, Enomoto A, Asai M, Asai N, Yamamoto E, Kajiyama H, Shibata K, Kikkawa F, Takahashi M.
  • Journal Title: Cancer Sci. Volume: 105 Issue: 5 Pages: 545-52
  • DOI: 10.1111/cas.12390
  • Peer Reviewed / Open Access
• [Journal Article] Detection of a Soluble Form of CD109 in Serum of CD109 Transgenic and Tumor Xenografted Mice. (2014)
  • Author(s): Sakakura H, Murakumo Y, Mii S, Hagiwara S, Kato T, Asai M, Hoshino A, Yamamoto N, Sobue S, Ichihara M, Ueda M, Takahashi M.
  • Journal Title: PLoS One Volume: 9 Issue: 1 Pages: e83385-e83385
  • DOI: 10.1371/journal.pone.0083385
  • Peer Reviewed
• [Journal Article] Small gastrointestinal stromal tumor in the stomach: identification of precursor for clinical gastrointestinal stromal tumor using c-kit and α-smooth muscle actin expression. (2013)
  • Author(s): Mikami T, Nemoto Y, Numata Y, Hana K, Nakada N, Ichinoe M, Murakumo Y, Okayasu I.
  • Journal Title: Hum Pathol. Volume: 44 Issue: 12 Pages: 2628-35
  • DOI: 10.1016/j.humpath.2013.07.020
  • Peer Reviewed
• [Journal Article] Association of D2-40 and MMP-1 expression with cyst formation in lung metastatic lesions of cutaneous angiosarcoma on the scalp: immunohistochemical analysis of 23 autopsy cases. (2013)
  • Author(s): Masuzawa M, Mikami T, Numata Y, Tokuyama W, Masuzawa M, Murakumo Y, Okayasu I, Katsuoka K.
  • Journal Title: Hum Pathol. Volume: 44 Issue: 12 Pages: 2751-9
  • DOI: 10.1016/j.humpath.2013.07.022
  • Peer Reviewed
• [Journal Article] 新規TGF-β1シグナル抑制因子CD109 同定、最近の知見、将来の展望． (2013)
  • Author(s): 村雲芳樹
  • Journal Title: 北里医学 Volume: 43 Pages: 9-22
  • NAID: 40019756536
  • Peer Reviewed
• [Journal Article] The REV7 subunit of DNA polymerase ζ is essential for primordial germ cell maintenance in the mouse. (2013)
  • Author(s): Watanabe, N., Mii, S., Asai, N., Asai, M., Niimi, K., Ushida, K., Kato, T., Enomoto, A., Ishii, H., Takahashi, M., Murakumo, Y.
  • Journal Title: J. Biol. Chem. Volume: 288 Issue: 15 Pages: 10459-10471
  • DOI: 10.1074/jbc.m112.421966
  • Peer Reviewed
• [Journal Article] RET finger protein expression is associated with prognosis in lung cancer with EGFR mutations. (2012)
  • Author(s): Iwakoshi A, Murakumo Y, Kato T, Kitamura A, Mii S, Saito S, Yatabe Y, Takahashi M.
  • Journal Title: Pathol Int Volume: 62 Pages: 324-330
  • Peer Reviewed
• [Journal Article] Involvement of Girdin in the determination of cell polarity during cell migration (2012)
  • Author(s): Ohara K, Enomoto A, et al.
  • Journal Title: PLoS One Volume: 7 Issue: 5 Pages: e36681-e36681
  • DOI: 10.1371/journal.pone.0036681
  • Peer Reviewed
• [Journal Article] The Dishevelled-associating protein Daple controls the non-canonical Wnt/Rac pathway and cell motility (2012)
  • Author(s): Ishida-Takagishi M, Enomoto A, et al.
  • Journal Title: Nat Commun Volume: 3 Issue: 1 Pages: 859-859
  • DOI: 10.1038/ncomms1861
  • Peer Reviewed
• [Journal Article] Exposure to 1-bromopropane induces microglial changes and oxidative stress in the rat cerebellum. (2012)
  • Author(s): Subramanian K, Mohideen SS, Suzumura A, Asai N, Murakumo Y, Takahashi M, Jin S, Zhang L, Huang Z, Ichihara S, Kitoh J, Ichihara G.
  • Journal Title: Toxicology. Volume: 302（1） Issue: 1 Pages: 18-24
  • DOI: 10.1016/j.tox.2012.07.006
  • Peer Reviewed
• [Journal Article] Epidermal Hyperplasia and Appendage Abnormalities in Mice Lacking CD109. (2012)
  • Author(s): Mii S, Murakumo Y, Asai N, Jijiwa M, Hagiwara S, Kato T, Asai M, Enomoto A, Ushida K, Sobue S, Ichihara M, Takahashi M.
  • Journal Title: Am J Pathol Volume: 181 Issue: 4 Pages: 1180-1189
  • DOI: 10.1016/j.ajpath.2012.06.021
  • Peer Reviewed
• [Journal Article] Similar phenotypes of Girdin germ-line and conditional knockout mice indicate a crucial role for Girdin in the nestin lineage (2012)
  • Author(s): Masato Asai
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 426 Issue: 4 Pages: 533-538
  • DOI: 10.1016/j.bbrc.2012.08.122
  • Peer Reviewed
• [Journal Article] Expression of RET finger protein predicts chemoresistance in epithelial ovarian cancer. (2012)
  • Author(s): Maiko Horio
  • Journal Title: Cancer Medicine Volume: 1 Issue: 2 Pages: 218-29
  • DOI: 10.1002/cam4.32
  • Peer Reviewed
• [Presentation] REV7, an Accessory Subunit of DNA Polymerase ζ Is Essential for Primordial Germ Cell Survival in the Mouse (2014)
  • Author(s): Yoshiki Murakumo, Naoki Watanabe, Shinji Mii, Naoya Asai, Masato Asai, Kaoru Niimi, Takuya Kato, Atsushi Enomoto, Hideshi Ishii, Masahide Takahashi
  • Organizer: Zinc conference, DNA polymerase
  • Place of Presentation: ケンブリッジ（イギリス）
  • Year and Date: 2014-08-31 – 2014-09-04
• [Presentation] CD109は神経膠芽腫細胞株SK-MG-１にてTGF-β1シグナル抑制的、EGFシグナル促進的に働く (2014)
  • Author(s): 村雲芳樹、三井伸二、高橋雅英
  • Organizer: 第１０３回日本病理学会総会
  • Place of Presentation: 広島国際会議場（広島）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] DNA修復蛋白REV7の新規結合蛋白の同定 (2014)
  • Author(s): 高村永梨奈、沼田賀子、梅沢敦子、蒋世旭、村雲芳樹
  • Organizer: 第１０３回日本病理学会総会
  • Place of Presentation: 広島国際会議場（広島）
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] Rev7は胎生期の始原生殖細胞の維持に必須である (2012)
  • Author(s): 渡辺直樹、村雲芳樹、三井伸二、浅井真人、浅井直也、高橋雅英：
  • Organizer: 第１０１回日本病理学会総会
  • Place of Presentation: 東京
• [Presentation] 肺癌におけるRET finger protein発現と予後に関する免疫組織学的検討 (2012)
  • Author(s): 岩越朱里、村雲芳樹、加藤琢也、北村彩、三井伸二、谷田部恭、高橋雅英
  • Organizer: 第１０１回日本病理学会総会
  • Place of Presentation: 東京
• [Presentation] TGF-β関連タンパク質CD109の新規腫瘍マーカーへの応用 (2012)
  • Author(s): 坂倉寛紀、村雲芳樹、三井伸二、萩原純孝、山本憲幸、上田実、高橋雅英
  • Organizer: 第７１回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] CD109ノックアウト/LacZノックインマウスにおける皮膚表現型の解析 (2012)
  • Author(s): 三井伸二、村雲芳樹、浅井直也、高橋雅英
  • Organizer: 第７１回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] マウス生殖細胞の維持におけるRev7の重要性
  • Author(s): 村雲芳樹、渡辺直樹、三井伸二、浅井直也、浅井真人、加藤琢也、榎本篤、高橋雅英
  • Organizer: 第１０２回日本病理学会総会
  • Place of Presentation: ロイトン札幌（札幌市中央区）
• [Presentation] 癌関連タンパク質CD109の新規血清腫瘍マーカーとしての可能性の検討
  • Author(s): 三井伸二、坂倉寛紀、村雲芳樹、市原正智、高橋雅英
  • Organizer: 第１０２回日本病理学会総会
  • Place of Presentation: ロイトン札幌（札幌市中央区）
• [Presentation] DNA修復蛋白Rev7はマウスの始原生殖細胞の維持のために必須である
  • Author(s): 村雲芳樹、三井伸二、浅井直也、新美薫、加藤琢也、榎本篤、高橋雅英
  • Organizer: 第７２回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜市西区）
• [Presentation] 卵巣明細胞癌においてREV7抑制によりシスプラチン感受性が増強する．
  • Author(s): 新美薫、村雲芳樹、吉川史隆、高橋雅英
  • Organizer: 第７２回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜市西区）
• [Presentation] がん細胞集団におけるLeading Cellを規定する分子機構の解明
  • Author(s): 加藤琢也、榎本篤、浅井真人、浅井直也、村雲芳樹、高橋雅英
  • Organizer: 第７２回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜市西区）
• [Book] ロビンス 基礎病理学 原書９版 (2014)
  • Author(s): 豊国伸哉、高橋雅英、村雲芳樹、他
  • Total Pages: 1021
  • Publisher: 丸善出版