Study on the abnormal centrosome regulation, leading to the chromosome instability in cancer

• Project/Area Number: 19790286
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: SHINMURA Kazuya Hamamatsu University School of Medicine, 医学部, 准教授 (40321880)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥3,800,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥600,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥1,200,000 (Direct Cost: ¥1,200,000)
• Keywords: 中心体 / 染色体不安定性 / がん / p53 / NORE1A / ベンゾピレン / 中心体過剰複製 / hSgo1 / 中心体サイクル / 非小細胞肺がん / EML4-ALK / がん抑制遺伝子 / P53 / B[a]PDE / hSgol / ヌクレオフオスミン / EML4 / SUMO化

Research Abstract

B[a]PDE, the ultimate carcinogenic metabolite of benzo[a]pyrene, contributes to neoplasia by inducing centrosome amplification and consequent chromosome destabilization as well as its mutagenic activity. hSgo1 is down-regulated in colorectal cancers and hSgo1 down-regulation leads to centrosome amplification and chromosome instability in colorectal cancer cells. The centrosomally localized p53 participates in the regulation of centrosome duplication in a manner independent of its transactivation function in addition to its transactivation-dependent regulation of centrosome duplication. NORE1A has activity that suppresses the centrosome amplification induced by hydroxyurea and NORE1A mRNA down-regulation is one of the common gene abnormalities in non-small cell lung carcinoma.

Research Products

• [Journal Article] EML4-ALK fusion transcripts in immunohistochemically ALK-positive non-small cell lung carcinomas. (2010)
  • Author(s): Shinmura K, Kageyama S, Igarashi H, Kamo T, Mochizuki T, Suzuki K, Tanahashi M, Niwa H, Ogawa H, Sugimura H
  • Journal Title: Exp Ther Med 1 Pages: 271-275
  • Peer Reviewed
• [Journal Article] EML4-ALK fusion transcripts in immunohistochemically ALK-positive non-small cell lung carcinomas (2010)
  • Author(s): Shinmura K, et al.
  • Journal Title: Exp Ther Med 1 Pages: 271-275
  • Peer Reviewed
• [Journal Article] Altered expression of the human base excision repair gene NTH1 in gastric cancer. (2009)
  • Author(s): Goto M, Shinmura K, Igarashi H, Kobayashi M, Konno H, Yamada H, Iwaizumi M, Kageyama S, Tsuneyoshi T, Tsugane S, Sugimura H
  • Journal Title: Carcinogenesis 30 Pages: 1345-1352
  • Peer Reviewed
• [Journal Article] Human Sgo1 downregulation leads to chromosomal instability in colorectal cancer. (2009)
  • Author(s): Iwaizumi M, Shinmura K, Mori H, Yamada H, Suzuki M, Kitayama Y, Igarashi H, Nakamura T, Suzuki H, Watanabe Y, Hishida A, Ikuma M, Sugimura H
  • Journal Title: Gut 58 Pages: 249-260
  • Peer Reviewed
• [Journal Article] Alterend expression of the human base excision repair gene NTH1 in gastric cancer (2009)
  • Author(s): Goto M, et al.
  • Journal Title: Carcinogenesis 30 Pages: 1345-1352
  • Peer Reviewed
• [Journal Article] Human Sgol down-regulation leads to chromosomal instability in human colorectal cancer cells (2009)
  • Author(s): Iwaizumi M, et.al.
  • Journal Title: Gut 58 Pages: 249-260
  • Peer Reviewed
• [Journal Article] Induction of centrosome amplification and chromosome instability in p53-deficient lung cancer cells exposed to benzo[a]pyrene diol epoxide (B[a]PDE). (2008)
  • Author(s): Shinmura K, Iwaizumi M, Igarashi H, Nagura K, Yamada H, Suzuki M, Fukasawa K, Sugimura H
  • Journal Title: J Pathol 216 Pages: 365-374
  • Peer Reviewed
• [Journal Article] Association between genetic polymorphisms of the base excision repair gene MUTYH and increased colorectal cancer risk in a Japanese population. (2008)
  • Author(s): Tao H, Shinmura K, Suzuki M, Kono S, Mibu R, Tanaka M, Kakeji Y, Maehara Y, Okamura T, Ikejiri K, Futami K, Yasunami Y, Maekawa T, Takenaka K, Ichimiya H, Imaizumi N, Sugimura H
  • Journal Title: Cancer Sci 99 Pages: 355-360
  • NAID: 10024002605
  • Peer Reviewed
• [Journal Article] EML4-ALK fusion transcripts, but no NPM-, TPM3-, CLTC-, ATIC-, or TFG-ALK fusion transcripts, in non-small cell lung carcinomas. (2008)
  • Author(s): Shinmura K, Kageyama S, Tao H, Bunai T, Suzuki M, Kamo T, Takamochi K, Suzuki K, Tanahashi M, Niwa H, Ogawa H, Sugimura H
  • Journal Title: Lung Cancer 61 Pages: 163-169
  • Peer Reviewed
• [Journal Article] Induction of centrosome amplification and chromosome instability in p53-deficient lung cancer cells exposed to benzo[a]pyrene diol epoxide (B[a]PDE) (2008)
  • Author(s): Shinmura K, et.al.
  • Journal Title: J Pathol 216 Pages: 365-374
  • Peer Reviewed
• [Journal Article] Association between genetic polymorphisms of the base excision repair gene MUTYH and increased colorectal cancer risk in a Japanese population (2008)
  • Author(s): Tao H, et.al.
  • Journal Title: Cancer Sci 99 Pages: 355-360
  • Peer Reviewed
• [Journal Article] Direct evidence for the role of centrosomally localized p53 in the regulation of centrosome duplication. (2007)
  • Author(s): Shinmura K, Bennett RA, Tarapore P, Fukasawa K
  • Journal Title: Oncogene 26 Pages: 2939-2944
  • Peer Reviewed
• [Journal Article] Sumoylation of nucleophosmin/B23 regulates its subcellular localization, mediating cell proliferation and survival. (2007)
  • Author(s): Liu X, Liu Z, Jang SW, Ma Z, Shinmura K, Kang S, Dong S, Chen J, Fukasawa, K, Ye K
  • Journal Title: Proc Natl Acad Sci USA 104 Pages: 9679-9684
  • Peer Reviewed
• [Journal Article] Identification and characterization of a novel germ line p53 mutation in familial gastric cancer in the Japanese population. (2007)
  • Author(s): Yamada H, Shinmura K, Okudela K, Goto M, Suzuki M, Kuriki K, Tsuneyoshi T, Sugimura H
  • Journal Title: Carcinogenesis 28 Pages: 2013-2018
  • Peer Reviewed
• [Journal Article] Direct evidence for the role of centrosomally localized p53 in the regulation of centrosome duplication (2007)
  • Author(s): Shinmura K, et. al.
  • Journal Title: Oncogene 26 Pages: 2939-2944
  • Peer Reviewed
• [Journal Article] Sumoylation of nucleophosmin/B23 regulates its subcellular localization,mediating cell proliferation and survival (2007)
  • Author(s): Liu X, et. al.
  • Journal Title: Proc Natl Acad Sci U S A 104 Pages: 9679-9684
  • Peer Reviewed
• [Journal Article] Identification and characterization of a novel germ line p53 mutation in familial gastric cancer in the Japanese population (2007)
  • Author(s): Yamada H, et. al.
  • Journal Title: Carcinogenesis 28 Pages: 2013-2018
  • Peer Reviewed
• [Journal Article] Suppression of hydroxyurea-induced centrosome amplification by NORE1A and down-regulation of NORE1A mRNA expression in non-small cell lung carcinoma.
  • Author(s): Shinmura K, Tao H, Nagura K, Goto M, Matsuura S, Mochizuki T, Suzuki K, Tanahashi M, Niwa H, Ogawa H, Sugimura H
  • Journal Title: Lung Cancer (in press)
  • Peer Reviewed
• [Journal Article] Suppression of hydroxyurea-induced centrosome amplification by NORE1A and down-regulation of NORE1A mRNA expression in non-small cell lung carcinoma
  • Author(s): Shinmura K, et al.
  • Journal Title: Lung Cancer (in press)
  • Peer Reviewed
• [Journal Article] EML4-ALK fusion transcripts,but no NPM-,TPM3-,CLTC-,ATIC-,or TFG-ALK fusion transcripts,in non-small cell lung carcinomas
  • Author(s): Shinmura K, et. al.
  • Journal Title: Lung Cancer (in press)
  • Peer Reviewed
• [Presentation] Altered expression of the human base excision repair gene NTH1 in gastric cancer. (2009)
  • Author(s): Goto M, Shinmura K, Igarashi H, Kobayashi M, Konno H, Yamada H, Iwaizumi M, Kageyama S, Tsuneyoshi T, Tsugane S, Sugimura H
  • Organizer: 68th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Yokohama
• [Presentation] 消化管癌におけるシュゴシン(hSgo1)の病理学的変化と染色体不安定性への関与. (2009)
  • Author(s): 岩泉守哉、新村和也、森弘樹、山田英孝、北山康彦、伊熊睦博、椙村春彦
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 京都
• [Presentation] ベンゾピレン代謝産物B[a]PDEを処理したp53欠損肺癌細胞株における中心体過剰複製と染色体不安定性の誘導. (2009)
  • Author(s): 新村和也、岩泉守哉、鈴木雅也、五十嵐久喜、山田英孝、椙村春彦
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 京都
• [Presentation] Production of a novel hSgo1 splicing product is a potential cause of down-regulation of wild type hSgo1 in colorectal cancer. (2009)
  • Author(s): Iwaizumi M, Shinmura K, Yamada H, Sugimura H
  • Organizer: 100th Annual Meeting of the American Association for Cancer Research.
  • Place of Presentation: Denver
• [Presentation] 大腸癌においてヒトSgo1の低下は染色体不安定性を誘導する (2008)
  • Author(s): 岩泉守哉、新村和也、伊熊睦博、椙村春彦
  • Organizer: 第16回浜名湖シンポジウム
  • Place of Presentation: 浜松
• [Presentation] Human Sgo1 down-regulation and chromosomal instability in colorectal cancer. (2008)
  • Author(s): Iwaizumi M, Shinmura K, Mori H, Yamada H, Kitayama Y, Ikuma M, Sugimura H
  • Organizer: 67th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Nagoya
• [Presentation] Induction of centrosome amplification and chromosome instability in p53-deficient lung cancer cells exposed to B[a]PDE. (2008)
  • Author(s): Shinmura K, Iwaizumi M, Suzuki M, Sugimura H
  • Organizer: 67th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Nagoya
• [Presentation] Induction of centrosome amplification and chromosome instability in p53-deficient lung cancer cells exposed to B[a]PDE (2008)
  • Author(s): Shinmura K, et.al.
  • Organizer: 67th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Nagoya
• [Presentation] Identification and characterization of a novel germ line p53 mutation in Japanese familial gastric cancer (2007)
  • Author(s): Yamada H, Shinmura K, Okudela K, Goto M, Suzuki M, Kuriki K, Tsuneyoshi T, Sugimura H
  • Organizer: 66th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Yokohama
• [Presentation] Human Sgo1 downregulation leads to chromosome instability in human colorectal cancer cells. (2007)
  • Author(s): Iwaizumi M, Shinmura K, Mori H, Yamada H, Ikuma M, Sugimura H
  • Organizer: 66th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Yokohama