1999 Fiscal Year Annual Research Report

テロメラーゼ機能・テロメア維持機構の解明とその臨床応用

Research Project

Project/Area Number	08265104
Research Institution	Hiroshima University
Principal Investigator	井出利憲広島大学, 医学部, 教授 (60012746)
Keywords	テロメア維持機構 / 染色体外テロメア断片DNA / テロメラーゼ / 不死化 / 癌診断
Research Abstract	テロメラーゼ非依存的テロメア維持機構は、テロメア維持機構の理解のために重要であるばかりでなく、ヒト癌の一部に見られることや、テロメラーゼ活性を持つ癌細胞をテロメラーゼ阻害剤で処理した時に耐性細胞として出現するなど、制癌の面でも重要である。本機構を有する細胞は、異常に長いテロメア末端(23kbp以上)を持つことが特長とされてきたが、実は2-4kbpと短く、これが染色体外テロメア断片DNA(ECTR-DNA)と大きな複合体を形成していることがわかった。細胞内では、このような複合体形成によって、DNAポリメラーゼによるテロメア延長が起きるものと推定された。ヒト線維芽細胞は、テロメラーゼ遺伝子導入だけでは不死化できず、不死化にはSV40のT抗原遺伝子の働きも必要であることがわかったが、必要とされる機能はT抗原機能の全部ではなく、T抗原機能のごく一部かあるいはt抗原機能で代行されものと推定するまでに限局された。これに対して、ヒト血管内皮細胞ではテロメラーゼ遺伝子導入だけで不死化する可能性が有ることがわかった。テロメア・テロメラーゼの高感度・定量的・簡便な測定法を改良し、肝組織において前癌組織の半数に、慢性肝疾患を含む非癌部より明らかに高い活性を認め、患者に対する対処への指針の一つになると考えられた。肝組織のテロメアは、年齢とともに、年1回程度の細胞分裂に相当する短縮を示した。慢性肝炎、肝硬変では年齢によらずテロメアは短く、中には分裂限界に近いサイズを示すケースも見られることなどが、初めて示された。このように、本研究の目標としたすべてについて大きな進展があり、テロメア・テロメラーゼと細胞の分裂寿命・不死化、癌の発生・進展に関する基礎的研究と、診断・治療に結び付ける応用的研究の両面にわたって、大きく寄与することができた。

Research Products
(16 results)

All Other

All Publications (16 results)

[Publications] Tahara,H., et al: "Immuno-histochemical detection of human telomerase catalytic component, hTERT, in human colorectal tumor and non-tumor tissue sections"Oncogene. 18. 1561-1567 (1999)
[Publications] Kitamoto,M. and Ide,T: "Telomerase activity in precancerous hepatic nodules"Cancer. 85. 245-246 (1999)
[Publications] Sugimoto,M, et al: "A new aspect of Epstein Barr virus-transformed human B-lymphoblastoid cell lines : senescence and immortalization"Mech.Aging.Dev.. 107. 51-60 (1999)
[Publications] Nakamura,A et al: "Four novel mutations of the Fanconi anemia group A gene(FAA) in Japanese patients"J.Hum.Genet. 44. 48-51 (1999)
[Publications] Kakuo,S. et al: "Human is a unique species among primates in terms of telomere length"Biochem.Biophys.Res.Commun. 263. 308-314 (1999)
[Publications] Yasui,W. et al: "Immunohistochemical detection of human telomerase reverse transcriptase in normal mucosa and precancerous lesions of the stomach"Jpn.J.Cancer Res.. 90. 589-595 (1999)
[Publications] Harada,K. et al: "Telomerase activity in central nervous system malignant limphoma"Cancer. 86. 1050-1055 (1999)
[Publications] Nakamura,Y. et al: "Simple, rapid, sensitive and quantitative detection of telomere repeats in cell lysate by hybridization protection assay(HPA)"Clin.Chem.. 45. 1718-1724 (1999)
[Publications] Sugimoto,M. et al: "Wrong use of "immortalization" for B-lympho-blastoid cell lines transformed by Epstein-Barr virus"J.Virol. 73. 9690-9691 (1999)
[Publications] Ishii,Y. et al: "Telomerase activity in hybrids between telomerase-negative and telomerase-positive immortal human cells is repressed in the defferent complementation groups but not in the same complementation group of immortality"Mech.Aging Dev.. 110. 175-193 (1999)
[Publications] Nakamura,Y. et al: "Quantitative re-evaluation of telomerase activity in cancerous and noncancerous gastrointestinal tissues"Mol.Carcinog.. 26. 312-320 (1999)
[Publications] Okui,M. et al: "APG-2 protein, a member of the heat shock protein 110 family, is expressed high in various tissues during the rat development, but exceptionally low in adult heart"Neurochem.Internatl.. (in press). (2000)
[Publications] Okui,M. et al: "MNB/DYRK gene cloned from the Down syndrome critical region is expressed high in rat brain and heart during development"Genomics. (in press). (2000)
[Publications] Takahashi,S. et al: "Expression of telomerase component genes in hepatocellular carcinomas"Eur.J.Cancer. (in press). (2000)
[Publications] Takaishi,H. et al: "Precancerous hepatic nodules had significant levels of telomerase activity by sensitive quantitation using hybridization protection assay"Cancer. (in press). (2000)
[Publications] Aikata,H. et al: "Telomere reduction in human liver tissues with age and chronic inflammation"Exp.Cell.Res.. (in press). (2000)

1999 Fiscal Year Annual Research Report

テロメラーゼ機能・テロメア維持機構の解明とその臨床応用

Principal Investigator

井出 利憲 広島大学, 医学部, 教授 (60012746)

Research Products

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

[Publications] Kitamoto,M. and Ide,T: "Telomerase activity in precancerous hepatic nodules"Cancer. 85. 245-246 (1999)

[Publications] Sugimoto,M, et al: "A new aspect of Epstein Barr virus-transformed human B-lymphoblastoid cell lines : senescence and immortalization"Mech.Aging.Dev.. 107. 51-60 (1999)

[Publications] Nakamura,A et al: "Four novel mutations of the Fanconi anemia group A gene(FAA) in Japanese patients"J.Hum.Genet. 44. 48-51 (1999)

[Publications] Kakuo,S. et al: "Human is a unique species among primates in terms of telomere length"Biochem.Biophys.Res.Commun. 263. 308-314 (1999)

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

[Publications] Harada,K. et al: "Telomerase activity in central nervous system malignant limphoma"Cancer. 86. 1050-1055 (1999)

[Publications] Nakamura,Y. et al: "Simple, rapid, sensitive and quantitative detection of telomere repeats in cell lysate by hybridization protection assay(HPA)"Clin.Chem.. 45. 1718-1724 (1999)

[Publications] Sugimoto,M. et al: "Wrong use of "immortalization" for B-lympho-blastoid cell lines transformed by Epstein-Barr virus"J.Virol. 73. 9690-9691 (1999)

[Publications] Ishii,Y. et al: "Telomerase activity in hybrids between telomerase-negative and telomerase-positive immortal human cells is repressed in the defferent complementation groups but not in the same complementation group of immortality"Mech.Aging Dev.. 110. 175-193 (1999)

[Publications] Nakamura,Y. et al: "Quantitative re-evaluation of telomerase activity in cancerous and noncancerous gastrointestinal tissues"Mol.Carcinog.. 26. 312-320 (1999)

[Publications] Okui,M. et al: "APG-2 protein, a member of the heat shock protein 110 family, is expressed high in various tissues during the rat development, but exceptionally low in adult heart"Neurochem.Internatl.. (in press). (2000)

[Publications] Okui,M. et al: "MNB/DYRK gene cloned from the Down syndrome critical region is expressed high in rat brain and heart during development"Genomics. (in press). (2000)

[Publications] Takahashi,S. et al: "Expression of telomerase component genes in hepatocellular carcinomas"Eur.J.Cancer. (in press). (2000)

[Publications] Takaishi,H. et al: "Precancerous hepatic nodules had significant levels of telomerase activity by sensitive quantitation using hybridization protection assay"Cancer. (in press). (2000)

[Publications] Aikata,H. et al: "Telomere reduction in human liver tissues with age and chronic inflammation"Exp.Cell.Res.. (in press). (2000)

井出利憲広島大学, 医学部, 教授 (60012746)