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Microsatellite instability and cyclooxygenase-2 expression in gastric carcinogensis.

机译：胃癌发生过程中微卫星的不稳定性和环氧合酶2的表达。

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摘要

Development of gastric cancer is believed to be a multi-step progression from chronic gastritis, glandular atrophy, intestinal metaplasia (IM), dysplasia and ultimately to carcinoma. However, the molecular mechanisms leading to gastric cancer development remain largely unknown. Recently, two mechanisms have been demonstrated to contribute to colorectal carcinogenesis, namely microsatellite instability (MSI) and cyclooxygenase-2 (COX-2) overexpression. MSI, a well-characterized phenotype that implicates underlying defect of DNA mismatch repair, is found to account for a subset of gastric tumors. On the other hand, over-expression of COX-2, an inducible form of prostaglandin synthase, is also frequently detected in gastrointestinal cancer. Intriguingly, tumors with MSI phenotypes or COX-2 overexpression present with contrasting clinicopathological features, which may suggest distinct cancer development pathways and possible differential responses to treatment. These series of experiments sought to elucidate the role of MSI and COX2 in the gastric carcinogenesis process. The results showed that both MSI and COX-2 were frequently detected in premalignant gastric lesions as well as in gastric cancer. Chronic H. pylori infection and p53 mutation play a crucial role in the overexpression of COX-2 in gastric cancer. Nevertheless, eradication of H. pylori alone did not appear to retard the progression of IM despite a modest reduction in COX-2 expression. On the other hand, the two mutL component of the DNA mismatch repair proteins (hPMS1 and hMLH1) interact to form a hetero-dimer in human gastric cells that support the importance of hMLH1 in the stabilization of this complex, and hence the integrity of DNA mismatch repair function. Lastly, gastric cancers with MSI phenotypes had significantly reduced COX-2 expression, which may have significant implications on their response to potential chemopreventive effects of COX-2 inhibitors. These series of experiments broaden the current understanding of the gastric carcinogenesis process and further support the role of intestinal metaplasia in this transformation pathway.
机译：胃癌的发展被认为是从慢性胃炎，腺体萎缩，肠化生（IM），不典型增生到癌症的多步发展。然而，导致胃癌发展的分子机制仍然是未知的。最近，已证明有两种机制可导致大肠癌发生，即微卫星不稳定性（MSI）和环氧合酶2（COX-2）过表达。 MSI是一种表征良好的表型，暗示了DNA错配修复的潜在缺陷，被认为是胃肿瘤的一部分。另一方面，在胃肠道癌症中也经常检测到COX-2的过度表达，这是前列腺素合酶的一种可诱导形式。有趣的是，具有MSI表型或COX-2过表达的肿瘤表现出截然不同的临床病理特征，这可能暗示着截然不同的癌症发展途径和对治疗的不同反应。这些系列实验试图阐明MSI和COX2在胃癌发生过程中的作用。结果表明，MSI和COX-2在胃癌前病变和胃癌中均被频繁检测到。慢性幽门螺杆菌感染和p53突变在胃癌中COX-2的过表达中起关键作用。然而，尽管COX-2表达适度降低，但仅根除幽门螺杆菌似乎并未阻碍IM的发展。另一方面，DNA错配修复蛋白的两个mutL成分（hPMS1和hMLH1）相互作用，在人胃细胞中形成异二聚体，从而支持hMLH1在稳定该复合物以及DNA完整性方面的重要性。失配修复功能。最后，具有MSI表型的胃癌显着降低了COX-2的表达，这可能对其对COX-2抑制剂潜在的化学预防作用的反应具有重要意义。这些系列实验拓宽了对胃癌发生过程的当前了解，并进一步支持了肠上皮化生在该转化途径中的作用。

著录项

  • 作者

    Leung, Wai-keung.;

  • 作者单位

    Chinese University of Hong Kong (People's Republic of China).;

  • 授予单位 Chinese University of Hong Kong (People's Republic of China).;
  • 学科 Health Sciences Medicine and Surgery.; Health Sciences Pathology.; Health Sciences Oncology.
  • 学位 M.D.
  • 年度 2001
  • 页码 237 p.
  • 总页数 237
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 病理学;肿瘤学;
  • 关键词

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