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Genomic analysis of mutational genetic events in the genes involved in gastroenterological cancer progression.

Research Project

Project/Area Number 13470114
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionThe University of Tokyo

Principal Investigator

ABURATANI Hiroyuki  The University of Tokyo, Center for Collaborative Research, Professor, 国際・産学共同研究センター, 教授 (10202657)

Co-Investigator(Kenkyū-buntansha) KODAMA Tatsuhiko  The University of Tokyo, Research Center for Advanced Science and Technology, Professor, 先端科学技術研究センター, 教授 (90170266)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥16,400,000 (Direct Cost: ¥16,400,000)
Fiscal Year 2003: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2002: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥8,800,000 (Direct Cost: ¥8,800,000)
Keywordsgene expression profiles / LOH / genomic analysis / cluster analysis / liver cancer / gastric cancer / 新規膜蛋白 / 膵癌 / マイクロアレイ / 腹膜播種 / WWOX / 肝細胞癌 / ガレクチン / 悪性化 / リンパ節転移
Research Abstract

To understand the multi-step carcinogenesis process, we have applied transcriptome analysis and genomic analysis to collect comprehensive biological information, then developed novel data analysis algorithms for mining such huge amount of data.
1) Molecular signature based on differentiation grade of hepatocellular carcinoma (HCC)
We applied the EIM (Expression Imbalance Map) to detect the chromosomal bias in gene expression profiles. The results were well correlated with previous reports by CGH and was also confirmed by quantitative PCR. We assume gene dosage has a significant effect on the gene expression profiles. We also observed chromosomal aberrations accumulate during the dedifferentiation process.
We demonstrated GPC3 protein level is elevated in HCCs as well as its RNA level. GPC3 inhibits BMP-7 signaling through the Smad pathway by reporter gene assay.
2) Molecular and functional analysis of the genes involved in gastric cancer progression
To gain molecular understanding of carcinogenesis, progression, and diversity of gastric cancer, 22 primary human advanced gastric cancer tissues and 8 noncancerous gastric tissues were analyzed by high-density oligonucleotide microarray in this study. These results provide not only a new molecular basis for understanding biological properties of gastric cancer, but also useful resources for future development of therapeutic targets and diagnostic markers for gastric cancer.
We performed global analysis on differential gene expression of a scirrhous gastric cancer cell line (OCUM-2M) and its derivative sublines with high potential for metastasis to the peritoneal cavity (OCUM-2MD3) and lymph nodes (OCUM-2MLN) We observed preferential up-regulation of trefoil factor 1, alpha-1-antitrypsin, and galectin 4 and down-regulation of cytidine deaminase in cells prone to peritoneal dissemination. Induction of Galectin4 in Tet-inducible Galectin4 expression cell line, MKN74TetOff-g4, elevation of mobility and invasion were observed.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Watanabe A, Hippo Y, Taniguchi H, Iwanari H, Yashiro M, Hirakawa K, Kodama T, Aburatani H.: "An Opposing View on WWOX Protein Function as a Tumor Suppressor."Cancer Research. 63(24). 8629-8633 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ge X, Tsutsumi S, Aburatani H, Iwata S.: "Reducing false positives in molecular pattern recognition."Genome Informatics. 14. 34-43 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Midorikawa Y, Ishikawa S, Iwanari H, Imamura T, Sakamoto H, Miyazono K, Kodama T, Makuuchi M, Aburatani H.: "Glypican-3, overexpressed in hepatocellular carcinoma, modulates FGF2 and BMP-7 signaling."Int J Cancer. 103(4). 455-465 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Midorikawa Y, Tsutsumi S, Taniguchi H, Ishii M, Kobune Y, Kodama T, Makuuchi M, Aburatani H.: "Identification of genes associated with dedifferentiation of hepatocellular carcinoma with expression profiling analysis."Jpn J Cancer Res. 93(6). 636-643 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hippo Y, Taniguchi H, Tsutsumi S, Machida N, Chong JM, Fukayama M, Kodama T, Aburatani H.: "Global gene expression analysis of gastric cancer by oligonucleotide microarrays."Cancer Research. 62(1). 233-240 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hippo Y, Yashiro M, Ishii M, Taniguchi H, Tsutsumi S, Hirakawa K, Kodama T, Aburatani H.: "Differential gene expression profiles of scirrhous gastric cancer cells with highly metastatic potential to peritoneum or lymph nodes."Cancer Research. 61. 889-895 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Watanabe A, Hippo Y, Taniguchi H, Iwanari H, Yashiro M, Hirakawa K, Kodama T, Aburatani H.: "An Opposing View on WWOX Protein Function as a Tumor Suppressor."Cancer Research. 63(24). 8629-8633 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ge X, Tsutsumi S, Aburatani H, Iwata S.: "Reducing false positives in molecular pattern recognition."Genome Informatics. 14. 34-43 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Midorikawa Y, Ishikawa S, Iwanari H, Imamura T, Sakamoto H, Miyazono K, Kodama T, Makuuchi M, Aburatani H.: "Glypican-3, overexpressed in hepatocellular carcinoma, modulates FGF2 and BMP-7 signaling."Int J Cancer. 103(4). 455-465 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Midorikawa Y, Tsutsumi S, Taniguchi H, Ishii M, Kobune Y, Kodama T, Makuuchi M, Aburatani H.: "Identification of genes associated with dedifferentiation of hepatocellular carcinoma wish expression profiling analysis."Jpn J Cancer Res. 93(6). 636-643 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hippo Y, Taniguchi H, Tsutsumi S, Machida N, Chong JM, Fukayama M, Kodama T, Aburatani H.: "Global gene expression analysis of gastric cancer by oligonucleotide microarrays."Cancer Research. 62(1). 233-240 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hippo Y, Yashiro M, Ishii M, Taniguchi H, Tsutsumi S, Hirakawa K, Kodama T, Aburatani H.: "Differential gene expression profiles of scirrhous gastric cancer cells with highly metastatic potential to peritoneum or lymph nodes."Cancer Research. 61. 889-895 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hippo Y, Watanabe K, Watanabe A, Midorikawa Y, Yamamoto S, Ihara S, Tokita S, Iwanari H, Ito Y, Nakano K, Nezu J, Tsunoda H, Yoshino T, Ohizumi I, Tsuchiya M, Ohnishi S, Makuuchi M, Hamakubo T, Kodama T, Aburatani H.: "Identification of Soluble Amino Terminal Fragment of Glypican-3 as a Serological Marker for Early Stage Hepatocellular Carcinoma"Cancer Research. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Joo A, Aburatani H, Morii E, Iba H, Yoshimura A.: "STAT3 and MITF cooperatively induce cellular transformation through upregulation of c-fos expression"Oncogene. 23(3). 726-734 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Watanabe A, Hippo Y, Taniguchi H, Iwanari H, Yashiro M, Hirakawa K, Kodama T, Aburatani H.: "An Opposing View on WWOX Protein Function as a Tumor Suppressor"Cancer Res. 63(24). 8629-8633 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kashima T, Nakamura K, Kawaguchi J, Takanashi M, Ishida T, Aburatani H, Kudo A, Fukayama M, Grigoriadis AE.: "Overexpression of cadherins suppresses pulmonary metastasis of osteosarcoma in vivo"Int J Cancer. 104(2). 147-154 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kano M, Nishimura K, Ishikawa S, Tsutsumi S, Hirota K, Hirose M, Aburatani H.: "Expression Imbalance Map : A New Visualization Method for Detection of mRNA Expression Imbalance Regions"Physiol Genomics. 13. 31-46 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Midorikawa Y, Ishikawa S, Iwanari H, Imamura T, Sakamoto H, Miyazono K, Kodama T, Makuuchi M, Aburatani H.: "Glypican-3, overexpressed in hepatocellular carcinoma, modulates FGF2 and BMP-7 signaling"Int J Cancer. 103(4). 455-465 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kano M, Nishimura K, Ishikawa S, Tsutsumi S, Hirota K, Hirose M, Aburatani H: "Expression Imbalance Map : A New Visualization Method for Detection of mRNA Expression Imbalance Regions"Physiol Genomics. Jan 7(epub ahead of print). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Midorikawa Y, Ishikawa S, Iwanari H, Imamura T, Sakamoto H, Miyazono K, Kodama T, Makuuchi M, Aburatani H: "Glypican-3, overexpressed in hepatocellular carcinoma, modulates FGF2 and BMP-7 signaling"Int J Cancer. 103(4):. 455-465 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Aburatani H.: "Understanding cancer through gene expression profiling. (review)"International Congress Series. 1246. 261-270 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Chong JM, Sakuma K, Sudo M, Osawa T, Ohara E, Uozaki H, Shibahara J, Kuroiwa K, Tominaga SI, Hippo Y, Aburatani H, Funata N, Fukayama M: "Interleukin-1 beta Expression in Human Gastric Carcinoma with Epstein-Barr Virus Infection"J. Virol.. 76(13):. 6825-6831 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Midorikawa Y, Tsutsumi S, Taniguchi H, Ishii M, Kobune Y, Kodama T, Makuuchi M, Aburatani H: "Identification of genes associated with dedifferentiation of hepatocellular carcinoma with expression profiling analysis"Jpn. J. Cancer Res.. 93(6):. 636-643 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hippo Y, Taniguchi H, Tsutsumi S, Machida N, Chong JM, Fukayama M, Kodama T, Aburatani H: "Global gene expression analysis of gastric cancer by oligonucleotide microarrays"Cancer Research. 62(1). 233-240 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takahashi M, et al.: "Fish oil feeding alters liver gene expressions to defend against PPARalpha activation and ROS production"Am J Physiol Gastrointest Liver Physiol. 282(2). 338-348 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hippo Y, et al.: "Global gene expression analysis of gastric cancer by oligonucleotide microarrays"Cancer Res.. 62(1). 233-240 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takabe W, et al.: "Anti-atherogenic antioxidants regulate the expression and function of proteasome alpha-type subunits in human endothelial cells"J Biol Chem. 276(44). 40497-40501 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Saiura A, et al.: "A comparison of gene expression in murine cardiac allografts and isografts by means DNA microarray analysis"Transplantation. 72(2). 320-329 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Akiyoshi S, et al.: "Targets of transcriptional regulation by transforming growth factor-beta : expression profile analysis using oligonucleotide arrays"Jpn J Cancer Res. 92(3). 257-268 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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