1999 年度実績報告書

テロメラーゼ関連遺伝子を用いたがんの新しい分子病理診断

研究課題

研究課題/領域番号	10470050
研究機関	広島大学
研究代表者	田原榮一広島大学, 医学部, 教授 (00033986)
研究分担者	横崎宏広島大学, 医学部, 講師 (10200891) 安井弥広島大学, 医学部, 助教授 (40191118)
キーワード	TRF / テロメア / テロメラーゼ / Tankyrase / 胃がん
研究概要	TRF1,2(telomeric-repeat binding factors)は、ヒト染色体末端のテロメアDNAに結合する蛋白質として知られており、TRF1はテロメア長を負に制御し、TRF2はテロメア末端を保護し染色体のend to end fusionを阻害する。また、TRF1のADP ribosyl化によりTRF1とテロメアDNAの結合を阻害し、テロメア長の調節に関与する蛋白質としてtankyrase(TRF1-interacting,ankyrin-related ADP-ribose polymerase)が報告されている。本研究では、ヒト胃癌組織20例において、これらテロメア構成因子の発現を解析し、また同時にテロメラーゼ活性、テロメア長、テロメラーゼ触媒サブユニットTERT、テロメラーゼRNA成分TERC、テロメラーゼ付属蛋白TEP1の発現との相関を調べ、癌化への関与を検討した。その結果、TRF1で10例(50%)、TRF2で13例(65%)、tankyraseで11例(55%)において、非腫瘍部粘膜に比較し腫瘍部でmRNA高発現が認められた。また、症例をテロメア長が2kbよりも長い群、短い群に分け比較すると、長テロメア群ではテロメラーゼ活性は低く、TRF1は低発現、tankyraseは高発現、一方、短テロメア群ではその逆の関係が認められた。TERT,TERC,TEP1発現との間には明らかな相関は見られなかった。以上より、癌細胞においてTRF1,2,tankyraseがテロメア長ならびにテロメラーゼ活性を制御している可能性が考えられる。

研究成果
(17件)

すべてその他

すべて文献書誌 (17件)

[文献書誌] Yasui,W.: "Immunohistochemical detection of human telomerase reverse transcriptase in normal mucosa and precancerous lesions of the stomach."Jpn J Cancer Res. 90. 589-595 (1999)
[文献書誌] Yokozaki,H.: "Effect of 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperaziny]-2(1H)-quinolinone (vesnarinone)on the growth of gastric cancer cell lines."Cancer Lett. 140. 121-128 (1999)
[文献書誌] Yokozaki,H.: "Alteration p73 gene preferentially in foveolar type gastric carcinomas."Int J Cancer. 83. 192-196 (1999)
[文献書誌] Kuniyasu,H.: "Relative expression of E-cadherin and type IV collagenase genes predicts disease outcome in patients with resectable pancreatic carcinoma."Clin Cancer Res. 5. 25-33 (1999)
[文献書誌] Tahara,H.: "Immuno-histochemical detection of human telomerase catalytic component,hTERT,in human colorectal tumor and non-tumor tissue sections."Oncogene. 18. 1561-1567 (1999)
[文献書誌] Naka,K.: "Effect of antisense human telomerase RNA transfection on the growth of human gastric cancer cell lines."Biochem Biophys Res Commun. 255. 753-758 (1999)
[文献書誌] Kitadai,Y.: "Evidence for the causal role of IL-8 in angiogenesis and tumorigenecity of human gastric carcinoma cells."Br J Cancer. 81. 647-653 (1999)
[文献書誌] Hiyama,T.: "Overexpression of human telomerase RNA is an early event in oesophageal carcinogenesis."Virchows Arch. 434. 483-487 (1999)
[文献書誌] Sato,S.: "Silencing of the CD44 gene by CpG methylation in a human gastric carcinoma cell line."Jpn J Cancer Res. 90. 485-489 (1999)
[文献書誌] Suzuki,T.: "Expression of the E2F family in human gastrointestinal carcinomas."Int J Cancer. 81. 535-538 (1999)
[文献書誌] Xu,X.C.: "Expression and up-regulation of retinoic acid receptor-beta is associated with retinoid sensitivity and colony formation in esophageal cancer cell lines."Cancer Res. 59. 2477-2483 (1999)
[文献書誌] Yasui,W.: "Expression of cell cycle regulating transcription factor E2F-1 in colorectal carcinomas."Pathobiol. 67. 174-179 (1999)
[文献書誌] Nakamura,Y.: "Possible posttranscriptional regulation in cancerous and non-cancerous gastrointestinal tissues by quantitative-evaluation of telomerase activity."Mol Carcinogenesis. 26. 312-320 (1999)
[文献書誌] Tahara,E.: "Molecular pathology of Early Cancer"IOS press. 481 (1999)
[文献書誌] Tahara,E.: "Gastritis"Lippincott Williams & Wilkins. (1999)
[文献書誌] Tahara,E.: "3rd International Gastric Cancer Congress"Monduzzi Editore. 872 (1999)
[文献書誌] Tahara,E.: "The principles and practice of gastrointestinal oncology,Part2. Management of Specific."Oxford University Press(in press).

1999 年度 実績報告書

テロメラーゼ関連遺伝子を用いたがんの新しい分子病理診断

研究代表者

田原 榮一 広島大学, 医学部, 教授 (00033986)

研究成果

[文献書誌] Yasui,W.: "Immunohistochemical detection of human telomerase reverse transcriptase in normal mucosa and precancerous lesions of the stomach."Jpn J Cancer Res. 90. 589-595 (1999)

[文献書誌] Yokozaki,H.: "Effect of 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperaziny]-2(1H)-quinolinone (vesnarinone)on the growth of gastric cancer cell lines."Cancer Lett. 140. 121-128 (1999)

[文献書誌] Yokozaki,H.: "Alteration p73 gene preferentially in foveolar type gastric carcinomas."Int J Cancer. 83. 192-196 (1999)

[文献書誌] Kuniyasu,H.: "Relative expression of E-cadherin and type IV collagenase genes predicts disease outcome in patients with resectable pancreatic carcinoma."Clin Cancer Res. 5. 25-33 (1999)

[文献書誌] Tahara,H.: "Immuno-histochemical detection of human telomerase catalytic component,hTERT,in human colorectal tumor and non-tumor tissue sections."Oncogene. 18. 1561-1567 (1999)

[文献書誌] Naka,K.: "Effect of antisense human telomerase RNA transfection on the growth of human gastric cancer cell lines."Biochem Biophys Res Commun. 255. 753-758 (1999)

[文献書誌] Kitadai,Y.: "Evidence for the causal role of IL-8 in angiogenesis and tumorigenecity of human gastric carcinoma cells."Br J Cancer. 81. 647-653 (1999)

[文献書誌] Hiyama,T.: "Overexpression of human telomerase RNA is an early event in oesophageal carcinogenesis."Virchows Arch. 434. 483-487 (1999)

[文献書誌] Sato,S.: "Silencing of the CD44 gene by CpG methylation in a human gastric carcinoma cell line."Jpn J Cancer Res. 90. 485-489 (1999)

[文献書誌] Suzuki,T.: "Expression of the E2F family in human gastrointestinal carcinomas."Int J Cancer. 81. 535-538 (1999)

[文献書誌] Xu,X.C.: "Expression and up-regulation of retinoic acid receptor-beta is associated with retinoid sensitivity and colony formation in esophageal cancer cell lines."Cancer Res. 59. 2477-2483 (1999)

[文献書誌] Yasui,W.: "Expression of cell cycle regulating transcription factor E2F-1 in colorectal carcinomas."Pathobiol. 67. 174-179 (1999)

[文献書誌] Nakamura,Y.: "Possible posttranscriptional regulation in cancerous and non-cancerous gastrointestinal tissues by quantitative-evaluation of telomerase activity."Mol Carcinogenesis. 26. 312-320 (1999)

[文献書誌] Tahara,E.: "Molecular pathology of Early Cancer"IOS press. 481 (1999)

[文献書誌] Tahara,E.: "Gastritis"Lippincott Williams & Wilkins. (1999)

[文献書誌] Tahara,E.: "3rd International Gastric Cancer Congress"Monduzzi Editore. 872 (1999)

[文献書誌] Tahara,E.: "The principles and practice of gastrointestinal oncology,Part2. Management of Specific."Oxford University Press(in press).

1999 年度実績報告書

田原榮一広島大学, 医学部, 教授 (00033986)