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Research on the abnormal expressions of bcl-xL and bak in gastrointestinal cancers

Research Project

Project/Area Number 10670470
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionOsaka University

Principal Investigator

KANAYAMA Shuji  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (40185913)

Co-Investigator(Kenkyū-buntansha) MIYAZAKI Yoshiji  Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30303960)
SHINOMURA Yasuhisa  Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90162619)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsGastric cancer / Colorectal cancer / Apoptosis / bcl-xL / bak / Missence mutation / IRF-1 / Stat3 / IRF-2 / アポト-シス / astat3
Research Abstract

The present research was designed to clarify how bcl-xL and bak are regulated in the gastrointestinal cancers.
Levels of bcl-xL, bak, IRF-1 and IRF-2 mRNAs were determined by a reverse transcription-polymerase chain reaction in endoscopic biopsy specimens from gastric and colorectal cancers. Enhanced expression of bcl-xL and reduced expression of bak were demonstrated in both gastric and colorctal cancers. In the colorectal cancers, expression of IRF-1 mRNA was significantly decreased. This decrease in the IRF-1 mRNA was negatively and positively correlated with bcl-xL and bak mRNAs, respectively. On the other hand, in the gastric cancers, no significant correlations were observed among their mRNA expressions. Abnormal expression of IRF-2 mRNAs were not observed in the gastric and colorctal cancers examined. These results suggest that abnormal regulation of bcl-xL and bak expressions are relevant to reduced expression of IRF-1 in colorectal cancers.
The oncogenic ras mutation is a common … More and critical step in gastrointestinal carcinogenesis. Oncogenic rastransfected intestinal epithelial cells showed an apoptosis resistance with Stat3 activation and bcl-xL increase.
The possible mutation of bak gene could play a significant role in the apoptosis resistance of cancers. We performed PCR-based single-strand conformational polymorphism and sequencing analysis of the entire cording lesion of the bak gene (exons 2-6) in 24 primary gastric cancers (6 early and 18 advanced cancers) and 20 primary colorectal cancers (6 early and 14 advanced cancers). Missense bak gene mutations were observed in 3 of 24 (12.5%) gastric cancers and 2 of 20 (10.0%) colorectal cancers. Sequence alterations without amino acid alteration were observed 1 of 24 (4.2%) gastric cancers and 2 of 20 (10.0%) colorectal cancers. Mutations in the bak gene were observed only in advanced gastrointestinal cancers but not in early stage carcinomas. These observations suggest that mutations in this gene predispose to the development of gastrointestinal malignancies in, at least, a subset of the cases. Less

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] M. Nakahara, et al.: "A novel gain-of-function mutation of c-kit gene in gastrointestinal stromal tumor"Gastroenterology. 115巻5号. 1090-1095 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S. Zushi, et al.: "STAT3 mediates the survival signal in oncogenic ras-transfected intestinal epithelial cells"Int. J. Cancer. 78巻3号. 326-130 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S. Kondo, et al.: "Modulation of Apoptosis by Endogenous Bcl-xL Expression in MKN-45 Human Gastric Cancer Cells"Oncogene. 17巻20号. 2585-2591 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kitamura S, et al.: "Peroxisome proliferator-activated receptor g induces growth arrest and differentiation markers of human colon cancer cells"Jpn. J. Cancer Res.. 90巻1号. 75-80 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miyazaki Y, et al.: "Gastrin induces heparin-binding epidermal growth factor-like growth factor in rat gastric epithelial cells transfected with gastrin receptor"Gastroenterology. 116巻1号. 78-89 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kitamura S, et al.: "PPARgamma inhibits the expression of c-Met in human gastric cancer cells through the supression of Ets."Biochem. Biophys. Res. Commun.. 265巻2号. 453-456 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M. Nakahara, K. Isozaki, S. Hirota, J. Miyagawa, M. Taniguchi, T. Nishida, S. Kanayama, Y. Kitamura, Y. Shinomura, Y. Matsuzawa: "A novel gain-of-function mutation of c-kit gene in gastrointestinal stromal tumor."Gastroenterology. 115(5). 1090-1095 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S. Zushi, Y. Shinomura, T. Kiyohara, Y. Miyazaki, S. Kondo, M. Sugimachi, Y. Higashimoto, S. Kanayama, Y. Matsuzawa: "STAT3 mediates the survival signal in oncogenic ras-transfected intestinal epithelial cells"Int. J. Cancer. 78(3). 326-330 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S. Kondo, Y. Shinomura, S. Kanayama, Y. Higashimoto, T. Kiyohara, S. Zushi, S. Kitamura, H. Ueyama, Y. Matsuzawa: "Modulation of Apoptosis by Endogenous Bcl-xL Expression in MKN-45 Human Gastric Cancer Cells."Oncogene. 17(20). 2585-2591 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y. Miyazaki, Y. Shinomura, S. Tsutsui, S. Kanayama, S. Hiraoka, Y. Matsuzawa: "Calphostin C induces expression of amphiregulin mRNA via reactive oxygen species in IEC-6 cells."Life Sci. 63(25). PL361-365 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y. Miyazaki, Y. Shinomura, S. Tsutsui, S. Zushi, Y. Higashimoto, S. Kanayama, S. Higashiyama, N. Taniguchi, Y. Matsuzawa: "Gastrin induces heparin-binding epidermal growth factor-like growth factor in rat gastric epithelial cells transfected with gastrin receptor."Gastroenterology. 116(1). 78-89 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S. Kitamura, Y. Miyazaki, Y. Shinomura, S. Kondo, S. Kanayama, Y. Matsuzawa: "Peroxisome proliferator-activated receptor g induces growth arrest and differentiation markers of human colon cancer cells."Jpn. J. Cancer Res. 90(1). 75-80 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S. Kitamura, Y. Miyazaki, S. Hiraoka, M. Toyota, Y. Nagasawa, S. Kondo, Y. Shinomura, Y. Matsuzawa: "PPARgamma inhibits the expression of c-MET in human gastric cancer cells through the supression of Ets."Biochem. Biophys. Res. Commun. 265(2). 453-456 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y. Nagasawa, Y. Miyoshi, K. Iwao, Y. Shinomura, Y. Matsuzawa, Y. Nakamura.: "Transformation and morphological changes of murine L cells by transfection with a mutated form of β-catenin."Cancer Res. 59. 3539-3542 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kitamura S.et al.: "Peroxisome proliferator-activated receptor g induces growth arrest and differentiation markers of human colon cancer cells"Jpn.J.Cancer Res.. 90巻1号. 75-80 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Miyazaki Y.et al.: "Gastrin induces heparin-binding epidermal growth factor-like growth factor in rat gastric epithelial cells transfected with gastrin receptor"Gastroenterology. 116巻1号. 78-89 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kitamura S.et al.: "PPAR gamma inhibits the expression of c-MET in human gastric cancer cells through the supression of Ets."Biochem.Biophys.Res.Commun.. 265巻2号. 453-456 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Murayama Y.et al.: "Morphological and functional restoration of parietal cells in helicobacter pylori associated enlarged fold gastritis after eradication"Gut. 45巻5号. 653-661 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kondo S.et al: "Modukation of apoptosis by endogenons Bcl-xL.expression in MKN-45 human gastric cancer cells." Oncogene. 17. 2585-2591 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Zushi S.et al: "Stat 3 mediates the survival signal in oncogenic ros-transfected intestinal epithelial cells." Int J Cancer. 78. 326-330 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakahara M.et al: "Anovel gain-of-function mutation of c-kit gene in gastrointestinal stromal tanor." Gastroenterology. 115. 1090-1095 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ueyama H.et al: "High Fas ligand expression on tymphocytes in lesions of ulcecative colitis." Gut. 43. 48-55 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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