Effects of telomerase and intracellular signal transduction pathways on carcinogenesis and development of colorectal carcinoma

端粒酶及细胞内信号转导通路对结直肠癌发生发展的影响

• 批准号: 08671442
• 负责人: TSUJITANI Shunichi
• 金额: $ 1.6万
• 依托单位: Tottori University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671442/
• 关键词: Colorectal cancer; Telomere; Telomerase; Genomic instability; Microsatellite; マイクロサテライト; テロメラーゼ活性; 遺伝子不安定性; 家族性大腸腺腫症; 多発癌

Telomeres of somatic cells are shortening with each cell division. While telomerase which involve the maintenance of telomere length is activated in malignant cells, and as a result, such cells aquire immortality. Mutations in mismatch repair genes result in a mutator phenotype that can be identified by observing microsatellite loci in nonfamilial colorectal cancer as well as hereditary non polyposis colorectal cancer. In this study, we investigated the telomerase activity and the microsatellite instability in nonfamilial colorectal cancers and adenomas. Telomerase activity was detected in 75% of colorectal cancers and in 33% of adenomas. Microsatellite instability was detected in 24% of sporadic cancers, in 54% of multiple cancers, and in 22% of colorectal adenomas. Telomerase activity and microsatellite instability ware independent events in colorectal carcinogenesis. The patients with telomerase activity and microsatellite instability showed poor prognosis. These results indicate that colorectal cancers with both telomerase activity and microsatellite instability may have more malignant potential, and adenomas with both telomerase activity and microsatellite instability may be more intensive precursor of colorectal cancers.

体细胞的端粒随着每次细胞分裂而缩短。而参与端粒长度维持的端粒酶在恶性细胞中被激活，从而使这些细胞获得永生。错配修复基因的突变导致一种增变子表型，这种表型可以通过观察非家族性结直肠癌和遗传性非息肉病性结直肠癌中的微卫星位点来识别。在这项研究中，我们调查了端粒酶活性和微卫星不稳定性在非家族性结直肠癌和腺瘤。75%的结直肠癌和33%的腺瘤中检测到端粒酶活性。在24%的散发性癌症、54%的多发性癌症和22%的结直肠腺瘤中检测到微卫星不稳定性。端粒酶活性和微卫星不稳定性是大肠癌发生的独立事件。端粒酶活性和微卫星不稳定的患者预后差。这些结果表明，同时具有端粒酶活性和微卫星不稳定性的结直肠癌可能具有更高的恶性潜能，同时具有端粒酶活性和微卫星不稳定性的腺瘤可能是更强烈的结直肠癌的前体。

项目成果

池口 正英: "家族性大腸腺腫症におけるテロメラーゼ活性" 消化器癌の発生と進展. 9. 85-88 (1997)

Masahide Ikeguchi：“家族性腺瘤性息肉病中的端粒酶活性”胃肠癌的发生和进展（1997）。

Ikeguchi, Masahide: "Telomerase activity in familial adenomatous polyposis" J Jpn Soc Gastroenterol. Carcinogen 9. 85-88 (1997)

Ikeguchi, Masahide：“家族性腺瘤性息肉病中的端粒酶活性”J Jpn Soc Gastroenterol。