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1998 Fiscal Year Final Research Report Summary

Relationship between genetic abnormalities of cell cycle regulators and genetic and chromosomal instabilities in gastrointestinal carcinomas

Research Project

Project/Area Number 08670204
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionHIROSHIMA UNIVERSITY

Principal Investigator

YASUI Watartu  Hiroshima University Faculty of Medicine, Associate professor, 医学部, 助教授 (40191118)

Project Period (FY) 1996 – 1998
KeywordsGastrointestinal carcinoma / Cell cycle regulators / Genetic instability / Telomerase / TERT / CyclinE / p27 / E2F-1
Research Abstract

1. Genetic and chromosomal instabilities in gastrointestinal carcinomas
Genetic instability (replication error : PER) was examined in the gastric carcinomas by microsatellite analysis, and was found in 30% of the cases. Especially, the instability at D 17S855 locus (near BRCA1) was frequent in younger patients. RER was also detected in a part of intestinal metaplasia next to gastric carcinoma. RER at more than two of the four loci was found in 3% of the gastric carcinomas, a half of which had multiple primary cancers.
Strong telomerase activity and increased hTR expression were detected in most of the gastric carcinomas and a portion of precancerous lesions. The telomerase activities were well correlated with the levels of TERT expression in most of the gastric and colorectal carcinomas. TERT expression was also detected in some of the adenomas and intestinal metaplasia of the stomach.
2. Genetic abnormalities of cell cycle regulators in gastrointestinal carcinomas
Gene amplification and o … More verexpression of cyclin E occurred frequently in the gastric and colorectal carcinomas that was closely related with high grade malignancy. About 70% of the gastric carcinomas expressed CDC25B at high levels. Reduced expression of p27, a CDK inhibitor, correlated well with aggressive behavior (advanced tumor stage, deeply invasion, and lymph-node metastasis) of the gastric and colorectal carcinomas. Gene amplification of E2F-1, an important target molecule of cell cycle regulators, was detected in 4% and 25% of the gastric and colorectal carcinomas, respectively. About 40% of the gastric carcinomas overexpressed E2F-1 mRNA.On the other hand, the expression of E2F-3 was reduced in 70% of the gastric carcinomas.
3. Relationship between telomerase and cell cycle regulators
Relationship between telomerase activity and the expression of various cyclins and CDK inhibitors in the gastric carcinomas. The expression of cyclin E tended to correlate with the telomerase activity, while no obvious tendency was detected between telomerase and the expression of p21 and p27. Less

  • Research Products

    (74 results)

All Other

All Publications (74 results)

  • [Publications] Kitahara K: "Expression of cyclin D1,CDK4 and p27KIP1 is associated with the p16MTS1 gene status in human esophageal carcinoma cell lines" Journal of Experimental Therapeutics and Oncology. 1・1. 7-12 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Semba S: "Microsatellite instability in precancerous lesions and adenocarcinomas of the stomach" Cancer. 77・8. 1620-1627 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akagi M: "Inhibition of cell growth by transforming growth factor betal is associated with p53-independent induction of p21 in gastric carcinoma cells" Japanese Journal of Cancer Research. 87・4. 377-384 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasui W: "Expression of cyclin E in human gastric adenomas and adenocarcinomas:correlation with proliferative activity and p53 status" Journal of Experimental Therapeutics and Oncology. 1・2. 88-94 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akama Y: "No point mutations but a codon 31 polymorphism and decreased expression of p21SDI1/WAF1/CIP1/MDA6 gene in human gastric carcinomas" Molecular and Cellular Differentiation. 4・2. 187-198 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akama Y: "Genetic status and expression of the cyclin-dependent kinase inhibitors in human gastric carcinoma cell lines" Japanese Journal of Cancer Research. 87・8. 824-830 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ito R: "Growth stimulatory effect of interleukin (IL)-la produced by oral squamous cell carcinoma cell lines" International Journal of Ocnology. 11・4. 807-812 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Naka K: "Growth inhibition of cultured human gastric cancer cells by 9-cis-retinoic acid with induction of cdk inhibitor Waf1/Cip1/Sdi1/p21 protein" Differentiation. 61・2. 313-320 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kudo Y: "Overexpression of CDK-activating CDC25B phosphatase in human gastric carcinomas" Japanese Journal of Cancer Research. 88・10. 947-952 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ito R: "Expression of IL-6 and its effect on the cell growth of gastric carcinoma cell lines" Japanese Journal of Cancer Research. 88・10. 953-958 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hamamoto T: "Altered microsatellites in incomplete-type intestinal metaplasia adjacent to primary gastric cancers" Journal of Clinical Pathology. 50・10. 841-846 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakahara M: "Identification of concurrent germ-line mutations in hMSH2 and/or hMLH1 genes in Japanese hereditary nonpolyposis colorectal cancer kindreds" Cancer Epidemiology,Biomarkers & Prevention. 6・6. 1057-1064 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasui W: "Expression of cyclin E in colorectal adenomas and adenocarcinomas:correlation with expression of Ki-67 antigen and p53 protein" Virchows Archiv. 429・1. 13-19 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasui W: "Expression of cyclin-dependent kinase inhibitor p21WAF1/CIP1 in non-neoplastic mucosa and neoplasia of the stomach:Relation with p53 status and proliferative activity" Journal of Pathology. 180・2. 122-128 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kuniyasu H: "Growth-inhibitory effect of interferon-beta is associated with the induction of cyclin-dependent kinase inhibitor,p27KIP1 in a human gastric carcinoma cell lines" Cell Growth & Differentiation. 8・1. 47-52 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kuniyasu H: "Expression of telomerase RNA is an early event of stomach carcinogenesis" Japanese Journal of Cancer Research. 88・2. 103-107 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasui W: "Expression of p21WAF1/CIP1 in colorectal adenomas and adenocarcinomas and its correlation with p53 protein expression" Pathology International. 47・6. 470-477 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasui W: "Reduced expression of cyclin-dependent kinase inhibitor p27Kip1 is associated with advanced stage and invasiveness of gastric carcinomas" Japanese Journal of Cancer Research. 88・7. 625-629 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kiriu H: "Microsatellite instability associated with primary head and neck cancers and secondary esophageal cancers" Japanese Journal of Clinical Oncology. 128・6. 733-739 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tahara H: "Immuno-histochemical detection of human telomerase catalytic component,hTERT,in human colorectal tumors and non-tumor tissue sections" Oncogene. in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suzuki T: "Expression of the E2F family in human gastrointestinal carcinomas" International Journal of Cancer. in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kitadai Y: "Expression of IL-8 correlates with vascularity in human gastric carcinomas" American Journal of Pathology. 152・1. 93-100 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shitara Y: "Mutation of the transforming growth factor-b type II receptor gene is rare ever in human gastric carcinomas" International Journal of Ocnology. 12・5. 1061-1065 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Semba S: "Frequent microsatellite instability and loss of heterozygosity in the region including BRCA1(17q21)in young patients with gastric cancer" International Journal of Ocnology. 12・6. 1245-1251 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamamoto S: "Expression of vascular endothelial growth factor in human gastric carcinomas" Pathology International. 48・7. 499-506 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasui W: "Expression of telemerase catalytic component,telemerase reverse transcriptase,in human gastric carcinomas" Japanese Journal of Cancer Research. 89・11. 1099-1103 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiyama T: "In situ mRNA hybridization technique for analysis of human telemerase RNA in gastric precancerous and cancerous lesions" Japanese Journal of Cancer Resarch. 89・11. 1187-1194 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tahara E: "Cell Proliferation in Cancer" Oxford University Press, 397 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasui W: "Recent Advances in Gastroenterological Carcinogenesis I" Monduzzi Editore, 1232 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 安井 弥: "スキルス胃癌の分子生物学" 医薬ジャーナル社, 226 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 安井 弥: "臨床腫瘍学" 癌と化学療法社(印刷中), (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 安井 弥: "新外科学体系(追補1)消化管の外科" 中山書店, 319 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yasui W: "Molecular Pathology of Gastrointestinal Cancer" Springer-Verlag, 267 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tahara E: "Molecular Pathology of Early Cancer" IOS Press in Press, (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tahara E: "Gastritis" Lippincott Williams & Wilkins in press, (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 安井 弥: "がんの浸潤・転移-基礎研究の臨床応用-" 医学書院, 329 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 安井 弥: "消化器疾患-state of arts Ver.2 I.胃・腸" 医歯薬出版, 533 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kitahara K: "Expression of cyclin D1, CDK4 and p27^<KTP1> is associated with the p16^<MTS1> gene status in human esophageal carcinoma cell lines" J Exp Therapeutics Oncol. 1(1). 7-12 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Semba S: "Microsatellite instability in precancerous lesions and adenocarcinomas of the stomach" Cancer. 77/8S. 1620-1627 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akagi M: "Inhibition of cell growth by transforming growth factor b1 is associated with p53-independent induction of p21 in gastric carcinoma cells" Jpn J Cancer Res. 87(4). 377-384 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasui W: "Expression of cyclin E in human gastric adenomas and adenocarcinomas : Correlation with proliferative activity and p53 status" J Exp Therapeutics Oncol. 1(2). 88-94 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akama Y: "No point mutations but a codon 31 polymorphism and decreased expression of p21^<SDI1/WAF1/CIP1/MDA6> gene in human gastric carcinomas" Mol Cell Differ. 4(2). 187-198 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akama Y: "Genetic status and exprssion the cyclin-dependent kinase inhibitors in human gastric carcinoma cell lines" Jpn J Cancer Res. 87(8). 824-830 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasui W: "Expression of cyclin E in colorectal adenomas and adenocarcinomas : Correlation with expression of Ki-67 antigen and p53 protein" Virchoes Archiv. 429(1). 13-19 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasui W: "Expression of cyclin-dependent kinase inhibitor p21^<WAF1/CIP1> in non-neoplastic mucosa and neoplasia of the stomach : Relation with p53 status and proliferative activity" J Pathol. 180(2). 122-128 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kuniyasu H: "Growyh-inhibitory effect of interferon-beta is associated with the induction of cyclin-dependent kibase inhibitor, p27KIP1 in a human gastric carcinoma cell line" Cell Growth & Differ. 8(1). 47-52 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kuniyasu H: "Expression of human telomerase RNA is an early event of stomach carcinogenesis" Jpn J Cancer Res. 88(2). 103-107 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasui W: "Expression of p21WAF1/CIP1 in colorectal adenomas and adenocarcinomas and its correlation with p53 protein expression" Pathol Int. 47(6). 470-477 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasui W: "Reduced expression of cyclin-dependent kinase inhibitor p27^<Kip1> is associated with advanced stage and invasiveness of gastric carcinomas" Jpn J Cancer Res. 88(7). 625-629 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito R: "Growth stimulatory effect of interleukin (IL) -la produced by oral squamous cell carcinoma cell limes" Int J Oncol. 11(4). 807-812 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Naka K: "Growth inhibition of cultured human gastric cancer cells by 9-cis-retinoic acid with induction of cdk inhibitor Waf1/Cip1/Sdi1/p21 protein" Differentiation. 61(2). 313-320 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kudo Y: "Overexpression of CDK-activating CDC25B phosphatase in human gastric carcinomas" Jpn J Cancer Res. 88(10). 947-952 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito R: "Expression of IL-6 and effect on the cell growth of gastric carcinoma cell lines" Jpn J Cancer Res. 88(10). 953-958 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hamamoto T: "Altered microsatellites in incomplete-type intestinal metaplasia adjacent to primary gastric cancers" J Clin Pathol. 50(10). 841-846 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakahara M: "Identification of concurrent germ-line mutations in hMSH2 and/or hMLH1 genes in Japanese hereditary nonpolyposis colorectal cancer kindreds" Cancer Epidemiol Biomarkers Prev. 6(6). 1057-1064 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kitadai Y: "Expression of IL-8 correlates with vascularity in human gastric carcinomas" Am J Pathol. 152(1). 93-100 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shitara Y: "Mutation of the transforming growth factor-beta type II receptor gene is rare event in human gastric carcinomas" Int J Oncol. 12(5). 1061-1065 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Semba S: "Frequent microsatellite instability and loss of heterozygosity in the region including BRCA1 (17q21) in young patients with gastric cancer" Int J Oncol. 12(6). 1245-1251 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamamoto S: "Expression of vascular endothelial growth factor in human gastric carcinomas" Pathol Int. 48(7). 499-506 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasui W: "Expression of telomerase catalytic component, telomerase reverse transcriptase, in human gastric carcinomas" Jpn J Cancer Res. 89(11). 1099-1103 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiyama T: "In situ mRNA hybridization technique for analysis of human telomerase RNA in gastric precancerous and cancerous lesions." Jpn J Cancer Res. 89(11). 1187-1194 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kiriu H: "Microsatellite instability associated with primary head and neck cancers and secondary esophageal cancers" Jpn J Clinical Oncol. 28(6). 733-739 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tahara H: "Immuno-histochemical detection of humsn telomerase catalytic component, hTERT,in human colorectal tumors and non-tumor tissue sections" Oncogene. (in press, 1999).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suzuki T: "Expression of the E2F family in human gastro-intestinal carcinomas" Int J Cancer. (in press, 1999).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tahara E: Cell Proliferation in Cancer. Oxford University Press, Oxford, (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasui W: Recent Advances in Gastroenterological Carcinogenesis I. Monduzzi Editore, Bologna, (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasui W: New Encyclopedia of Surgical Science (in Japanese). Nakayama-Shoten Co., Tokyo, (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasui W: Molecular Pathology of Gastrointestinal Cancer-Application to Clinical Practice-. Springer-Verlag, Yokyo, (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasui W: Scirrhous Gastric Cancer-Basic and clinical science- (in Japanese). Iyaku Journal co., Tokyo, (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasui W: Clinical Oncology (in Japanese). Cancer and Chemotherapy Publishers, Inc. (in press), (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasui W: Cancer Invasion and Metastasis (in Japanese). Igakushoin Co., Tokyo, (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yasui W: Digestive diseases-state of arts, Vol.I Stomach and intestine (in Japanese). Ishiyaku Publishers, Inc., Tokyo, Japan,

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tahara E: Molecular Pathology of Early Cancer. IOS Press, Amsterdem (in press), (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tahara E: Gastritis. Lippincott Williams & Wilkins, Philadelphia (in Press), (1999)

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

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Published: 1999-12-08  

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