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1999 Fiscal Year Final Research Report Summary

ELUDICATION OF ASSOCIATION AND SIGNAL TRANSDUCTION PATHWAY BETWEEN BETA-KATENIN AND GROWTH FACTOR RECEPTOR AT THE CANCER INVASION

Research Project

Project/Area Number 09470056
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionNational Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East

Principal Investigator

OCHIAI Atsushi  National Cancer Center Research Institute East, Pathology Division, Chief, 支所・臨床腫瘍病理部, 部長 (60183034)

Co-Investigator(Kenkyū-buntansha) KANAI Yae  National Cancer Center Research Institute East, Pathology Division, Head., 支所・臨床腫瘍病理部, 室長 (00260315)
NAKANISHI Hiroyuki  National Cancer Center Research Institute East, Pathology Division, Researcher, 支所・臨床腫瘍病理部, 主任研究官 (10260316)
SAKAMOTO Michiie  National Cancer Center Research Institute East, Pathology Division, Chief, 支所・臨床病理部, 部長 (40221270)
Project Period (FY) 1997 – 1999
Keywordsβ-catenin / Growth factor receptor / Signal transduction / Cell adhesion system / Invasion / Tyrosine phosphorylation
Research Abstract

1) Down regulation of the cadherin-mediated cell adhesion and tyrosine phosphoryaltion of β-catenin was stimulated by growth factors as epidermal growth factor (EGF) and transforming growth factor α (TGF α) using human cancer cell lines. Tyrosine phosphrylation of β-catenin was confirmed to be present in human colon cancer tissue at the invasive front where cancer cells dissociate from cancer nests in a single cells.
2) Physical association between β-catenin and c-erB-2 was confirmed using deletion mutants of β-catenin. The 12th armadillo repeat which locates at the center of β-catenin was found to bind the growth factor receptors as EGF receptor and c-erB-2. Tyrosine phosphoryaltion of the 12th armadillo repeat was occurred by EGF and TGF α stimulation. These results indicate the presence of signal transduction pathway between growth factor receptor and β-catenin.
3) A monoclonal antibody which recognizes tyrosine phosphorylated 12th armadillo repeat of β-catenin was generated using tyrosine phosphoryalted peptides. This antibody allows us to analyze the molecular mechanism of dysfunction of cadherin-mediated cell adhesion system through the growth factor receptor that activation of growth factor receptor phosphoryaltes β-catenin and stimulates dissociation between α and β-catenin.
4) Immunohistochemical staining of β-catenin in human colon cancer tissues showed that tyrosine phosphorylation of b-catenin at the 12th armadillo repeat specifically occurs at the invasive front where cancer cells dissociate from cancer nests. These results confirm the presence of signal transduction pathway between growth factor receptor and β-catenin in human cancer tissues and importance of this signal transduction in the cancer invasion and metastasis.

  • Research Products

    (47 results)

All Other

All Publications (47 results)

  • [Publications] Emura, M., Ochiai A., et al.: "In vitro reconsitution of human respiratory epithelium"In Vitro Cell Dev. Biol.. 33. 602-605 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Minamoto, T., Ochiai A. et al.: "Combined analysis of microsatellite instability and K-ras muatation incease detection incidence of normal samples from colorectal cancer patients"Clincal Cancer Res.. 3. 1413-1417 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanai Y. Ochiai, a., et al.: "The E-cadherin gene is silenced by CpG methylation in human hepatocellular carcinomas"Int. J. Cancer. 71. 355-359 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Naknishi, Y., Ochiai, A et al.: "Expression of E-cadherin, α-catenin, β-catenin and plakoglobin in esophageal carcinomas and its prognostic significance"Oncology. 54. 158-165 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasui, N., Ochiai, A., et al.: "Tumor growth and metastasis of human colorectal cancer cell lines in SCID mice resemble clinical metastatic behaviors"Invesion and Metasatsis. 17. 259-269 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Naknishi, Y., Ochiai, A et al.: "Clinicolathological significance of small Lugol's Iodine Unstained areas in the mucosa surrounding resected esophageal cancer"Cancer. 82. 1454-1459 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akimoto, S., Ochiai, A., et al.: "Expression of Cadherin- catenin cell adhesion molecules, phoaphorylated tyrosine residues and growth factor receptor-tyrosine kinases in gastric cancers"Jpn. J. Cancer Res.. 89. 829-836 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Inomata, M., Ochiai, a., et al.: "Macroscopic features at the deepest site of tumor penetration predicting liner metastases of colorectal cancer"Jpn. J. Clin. Oncol.. 28. 123-128 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanai Y., Ochiai A., et al.: "DNA hypermenthylation at the D17S5 locus is associated with gastric carcinogenesis"Cancer Letters. 122. 135-141 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kurisu Y., Ochiai A., et al.: "Histlogic and immunohistrochemical analysis of early submucosal invasive carcinoma of the colon and rectum"Pathol. Int.. 49. 608-616 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Harabayashi, T., Ochiai A., et al.: "Reduction of integrin b4 and enhanced migration on laminin in association with intraepithelial spreading of urinary bladder carcinoma"J Urology.. 161. 1364-1371 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Saito A., Ochiai A., et al.: "Disruption of E-cadherin-mediated cell adhesion system in young patients with cancers"Jpn. J. Cancer Res.. 90. 993-999 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimura K., Ochiai A., et al.: "Familial gastric cancer : clinicopathological characteristics, RER phenotype and germline p53 and E-cadherin mutations"Carcinogenesis. 20. (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Naknishi, Y., Ochiai, A et al.: "Clinical implication of lymph node mecrometastases in pstients with colorectal cancers. A case control study"Oncology. 57. (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Becker K-F., Ochiai A., et al.: "Analysis of E-cadherin in diffuse type gastric cancer using an mutation-specific monconal antibody"Am. J. Pathol.. 156. (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Konishi, K., Ochiai A., et al.: "Clinicolathological differences between colonic and recatl carcinomas : are they based on the same mechaism of carcinogenesis?"Gut. 45. 818-821 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Emura M., Ochiai A., et al.: "Development of myofibroblasts from human bone marrow mesenchymal atem cells co-cultured with human colon carcinomas and TGF beta 1"In Vitro Cell Dev. Biol.. 36. 77-80 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishii Y, Ochiai A., et al.: "Integin b4 as a suppressor and a predictive marker for peritoneal dissemination in humann gastric cancer"Gastroenterology. 118. 197-506 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hasebe T., Ochiai A., et al.: "Proliferative activity of intratumoral fibroblasts closely correlated with lymph node and distant organ mentastases of invasive ductal carcinoma of the breast"Am J Pathol.. (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hasebe T., Ochiai A., et al.: "Histopathological findings predicting lymph node metastasis and prognosis in patients with superficial esopahgeal cancer. Analysis of 240 surgically resected tumors"Cancer. 88. 1285-1293 (200)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ochiai A., et al.: "Gastric cancer"Oxford University Press, Oxford New York. 309 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ochiai A., et al.: "Molecular pathology of gastrointestinal cancer : application to clinical practice"springer Verag, Tokyo. 259 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ochiai A., Kanai, Y. et al.: "Epithelial morphogenesis and diseases."W and C Birchmeyer. 489 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Emura M., Ochiai A., et al.: "In vitro reconstitution of human respiratory epithelium."In vitro Cell Dev. Biol.. 33. (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Minamoto T., Ochiai A. et al.: "Combined analysis of microsatellite instability and K-ras muatation incease detection incidence of normal samples from colorectal cancer patients."Clincal Cancer Res.. 3. (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kanai Y. Ochiai, A., et al.: "The E-cadherin gene is silenced by CpG methylation in human hepatocellular carcinomas."Int. J. Cancer. 71. (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] nakanishi, Y., Ochiai, A. et al.: "Expression of E-cadherin, a-catenin, __-catenin and plakoglobin in esophageal carcinomas and its prognostic significance."Oncology,. 54. (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasui N., Ochiai A., et al.: "Tumor growth and metastasis of human colorectal cancer cell lines in SCID mice resemble clinical metastatic behaviors."Invesion and Metasatsis. 17. (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] nakanishi Y., Ochiai A., et al.: "Clinicopathological significance of small Lugol's Iodine Unstained areas in the mucosa surrounding resected esophageal cancer."Cancer. 82. (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akimoto S., Ochiai A., et al.: "Expression of Cadherin-catenin cell adhesion molecules, phosphorylated tyrosine residues and growth factor receptor-tyrosine kinases in gastric cancers."Jpn. J. Cancer Res.. 89. (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Inomata M., Ochiai A., et al.: "Macroscopic features at the deepest site of tumor penetration predicting liver metastases of colorectal cancer."Jpn. J. Clin. Oncol.. 28. (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kanai Y., Ochiai A., et al.: "DNA hypermethylation at the D17S5 locus is associated with gastric carcinogenesis."Cancer Letters. 122. (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kurisu Y., Ochiai A., et al.: "Histlogic and immunohistochemical analysis of early submucosal invasive carcinoma of the colon and rectum."Pathol Int.,. 49. (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Harabayashi T., Ochiai A., et al.: "Reduction of integrin b4 and enhanced migration on laminin in association with intraepithelial spreading of urinary bladder carcinoma."J Urology.. 161. (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Saito A., Ochiai A., et al.: "Disruption of E-cadherin-mediated cell adhesion system in young patients with gastric cancers."Jpn. J Cancer Res.. 90. (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimmura K., Ochiai A., et al.: "Familial gastric cancer: clinicopathological characteristics, RER phenotype and germline p53 and E-cadherin mutations."Carcinogenesis. 20. (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakanishi Y., Ochiai A., et al.: "Clinical implications of lymph node mecrometastases in patients with colorectal cancers. A case control study."Oncology. 57. (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Becker K-F., Ochiai A., et al.: "Analysis of E-cadherin in diffuse type gastric cancer using an mutation-specific monoclonal antibody."Am. J Pathol.. 156. (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Konishi, K, Ochiai A., et al.: "Clinicopathlogical differences between colonic and recatl carcinomas: are they based on the same mechanism of carcingogenesis?"Gut. 45. (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Emura M., Ochiai A., et al.: "Development of myfibroblasts from human bone marrow mesenchymal stem cells co-cultured with human colon carcinoma cells and TGF beta 1."In Vitro Cell Dev. Biol.. 36. (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishii. Y., Ochiai A., et al: "Integrin b4 as a suppressor and a predictive marker for peritoneal dissemination in human gastric cancer."Gastroenterology. 118. (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hasebe T., Ochiai A., et al.: "Proliferative activity of intratumoral fibroblats is closely correlated with lymph node and distant organ metastases of invasive ductal carcinoma of the breast."Am J Pathol.. (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hasebe T., Ochiai A., et al.: "New prognostic histological parameter of invasive ductal carcinoma of the breast: clinicopathological significance of fibrotic focus."Pathol. Int.. (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tajima Y., Ochiai A., et al.: "Histopathological findings predicting lymph node metastasis and prognosis in patients with superficial esopahgeal cancer."Analysis of 240 surgically resected tumors-. Cancer. 88. (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ochiai, A. et al.: "Multiple genetic alterations in gastric cancer."In "Gastric Cancer" T. Sugimura and M. Sasako ed.. 87-99 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ochiai A. et al.: "Genetic alterations In the precursors of gastric cancer."In "Molecular Pathology of Gastroenterological Cancer-Application to Clinical Practice". 43-54 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ochiai, A. et al.: "Multiple mechanisms for inactivation of E-cadherin cell adhesion system in cancer."In "Epithelial morphogenesis and diseases" W and C Birchmeyer. ed.. 427-444 (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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