Interaction between telomerase and histone acetylation in gastrointestinal carcinomas

胃肠道癌中端粒酶与组蛋白乙酰化的相互作用

基本信息

  • 批准号:
    11670175
  • 负责人:
  • 金额:
    $ 2.18万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    1999
  • 资助国家:
    日本
  • 起止时间:
    1999 至 2000
  • 项目状态:
    已结题

项目摘要

1. Histone acetylation status in gastrointestinal carcinomasReduced expression of acetylated histone H4 (low acetylation status) was detected in 66% of gastric cancers, 46% of gastric adenomas, 78% of colorectal cancers, and 30% of colorectal adenomas, respectively. Histone deacetylase inhibitor (trichostatin A : TSA) inhibited cell growth and induced apoptosis in gastric cancer cell lines, while TSA induced the expression of p21, CBP, BAK and cyclin E.Introduction of demethylase (MBD2) into gastric cancer cell line or TSA treatment retrieved the expression of CD44 and p16, while HDAC1 expression was suppressed. Interaction between histone acetylation and DNA methylation may be involved in gastrointestinal carcinogenesis through modulation of gene expression related to proliferation and apoptosis.2. Telomerase and telomere DNA interacting molecules in gastrointestinal carcinomasStrong telomerase activity and increased TERT expression were detected in most of the gastrointestinal carcin … More omas. 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. Increased expression of TRF1, TRF2 and tankyrase was detected in 50-60% of gastric carcinomas. The expression of TIN2 and hRAP1 was increased in 30% and 65% of gastric carcinomas, respectively. MRE11 complex consists of MRE11, RAD50 and NBS1 which acts as DNA repair enzyme. Increased expression of MRE11 RAD50 and NBS1 was found in 65%, 70% and 80% of gastric carcinomas, respectively.3. Relationship between histone acetylation and telomerase in gastrointestinal carcinomasMajorities of gastrointestinal carcinomas and a portion of precancerous lesions revealed low levels of histone acetylation and strong telomerase activity with increased TERT expression, suggesting that their interaction may deeply participate in gastrointestinal carcinogenesis at early stage. Less
1. 胃肠道癌中组蛋白乙酰化状态组蛋白H4乙酰化表达降低(低乙酰化状态)分别在66%的胃癌、46%的胃腺瘤、78%的结直肠癌和30%的结直肠腺瘤中检测到。组蛋白去乙酰化酶抑制剂(trichostatin A: TSA)在胃癌细胞系中抑制细胞生长并诱导细胞凋亡,TSA诱导p21、CBP、BAK和cyclin e的表达。将去甲基化酶(MBD2)引入胃癌细胞系或TSA处理后,CD44和p16的表达恢复,而HDAC1的表达受到抑制。组蛋白乙酰化和DNA甲基化的相互作用可能通过调节与增殖和凋亡相关的基因表达参与胃肠癌的发生。端粒酶和端粒DNA相互作用分子在胃肠道癌中的作用端粒酶活性强,TERT表达增高。端粒酶活性与TERT表达水平在大多数胃癌和结直肠癌中有良好的相关性。在部分胃腺瘤和肠化生中也检测到TERT的表达。在50-60%的胃癌中,TRF1、TRF2和tankyase的表达升高。胃癌中TIN2和hRAP1的表达分别升高30%和65%。MRE11复合体由MRE11、RAD50和作为DNA修复酶的NBS1组成。MRE11、RAD50和NBS1的表达分别在65%、70%和80%的胃癌中升高。胃肠道癌中组蛋白乙酰化与端粒酶的关系大多数胃肠道癌和部分癌前病变中组蛋白乙酰化水平低,端粒酶活性强,TERT表达增高,提示两者的相互作用可能在早期深度参与了胃肠道癌的发生。少

项目成果

期刊论文数量(44)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Tahara.H.: "Immuno-histochemical detection of human telomerase catalytic component, hTERT, in human colorectal tumors and non-tumor tissue sections"Oncogene. 18. 1561-1568 (1999)
Tahara.H.:“人结直肠肿瘤和非肿瘤组织切片中人端粒酶催化成分 hTERT 的免疫组织化学检测”癌基因。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
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  • 通讯作者:
Hayashi,K.: "Overexpression of retinoic acid receptor beta induces growth arrest and apoptosis in oral cancer cell lines"Japanese Journal of Cancer Research. 92. 42-50 (2001)
Hayashi,K.:“视黄酸受体β的过度表达会诱导口腔癌细胞系的生长停滞和凋亡”,《日本癌症研究杂志》。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Yokozaki, H.: "Alterations of p73 preferentially occur in gastric adenocarcinomas with foveolar epithelial phenotype."Int J Cancer. 83. 192-196 (1999)
Yokozaki, H.:“p73 的改变优先发生在具有小凹上皮表型的胃腺癌中。”Int J Cancer。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Nakamura, Y.: "Quantitative reevaluation of telomerase activity in cancerous and non-cancerous gastrointestinal tissues."Mol Carcinogenesis. 26. 312-320 (1999)
Nakamura, Y.:“对癌性和非癌性胃肠道组织中端粒酶活性的定量重新评估。”Mol 癌发生。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Nakamura,Y.: "Quantitative reevaluation of telomerase activlty in cancerous an non-cancerous gastrointestinal tissues"Molecular Carcinogenesis. 26・4. 312-320 (1999)
Nakamura,Y.:“癌性和非癌性胃肠道组织中端粒酶活性的定量重新评估”分子癌发生26・4(1999)。
  • DOI:
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  • 影响因子:
    0
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YASUI Watartu其他文献

YASUI Watartu的其他文献

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{{ truncateString('YASUI Watartu', 18)}}的其他基金

Relationship between genetic abnormalities of cell cycle regulators and genetic and chromosomal instabilities in gastrointestinal carcinomas
细胞周期调节因子的遗传异常与胃肠癌遗传和染色体不稳定性的关系
  • 批准号:
    08670204
  • 财政年份:
    1996
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

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