文章：

胃泌素是胃癌发生的积极参与者还是旁观者？

Gastrin — active participant or bystander in gastric carcinogenesis?

原文发布日期：2006-12-01

DOI: 10.1038/nrc2014

类型: Review Article

开放获取: 否

要点：

1. Coordinated activity between somatostatin and gastrin-releasing peptide (GRP) regulates secretion of gastrin from G cells in a negative and positive manner, respectively, to facilitate the release of gastric acid from parietal cells.
2. In transgenic mouse models, hypergastrinaemia contributes to the development of atrophy in the proximal gastric mucosa through the induction of parietal cell apoptosis, leading to the development of gastric adenocarcinoma. This phenomenon has not been confirmed in human gastric cancer.
3. Infection with Helicobacter pylori is associated with increased gastrin levels in serum and components of the bacterium might activate the gastrin promoter directly and indirectly. Conversely, infection with H. pylori reduces somatostatin activity. Furthermore, GRP, somatostatin and gastrin seem to modulate the inflammatory response to the bacterium.
4. Gastrin and GRP have well-documented pro-carcinogenic roles, particularly in animal models, that affect proliferation, angiogenesis and apoptosis, whereas the potential pro-apoptotic signal of somatostatin is lost during carcinogenesis owing to weak expression of somatostatin receptor isoforms.
5. Clinical agonists and antagonists of the three hormones have shown modest activity in patients with gastrointestinal cancer, and rational combinations of these agents might prove to be more clinically beneficial.

要点翻译：

1. 生长抑素和胃泌素释放肽（GRP）之间的协同活动分别以负向和正向方式调节G细胞中胃泌素的分泌，从而促进壁细胞释放胃酸。
2. 在转基因小鼠模型中，高胃泌素血症通过诱导壁细胞凋亡，导致近端胃黏膜发生萎缩，进而发展成胃腺癌。这一现象在人类胃癌中尚未得到证实。
3. 幽门螺杆菌感染与血清中胃泌素水平升高相关，该菌的某些成分可能直接或间接激活胃泌素启动子。相反，幽门螺杆菌感染会降低生长抑素活性。此外，GRP、生长抑素和胃泌素似乎能够调节对该菌的炎症反应。
4. 胃泌素和GRP具有明确记录的促癌作用（尤其在动物模型中），影响增殖、血管生成和凋亡过程；而生长抑素潜在的促凋亡信号在致癌过程中因生长抑素受体亚型表达微弱而丧失。
5. 这三种激素的临床激动剂和拮抗剂在胃肠道癌患者中显示出有限活性，但这些药物的合理组合可能会带来更具临床意义的获益。

英文摘要：

Gastrin is a pro-proliferative, anti-apoptotic hormone with a central role in acid secretion in the gastric mucosa and a long-standing association with malignant progression in transgenic mouse models. However, its exact role in human gastric malignancy requires further validation. Gastrin expression is tightly regulated by two closely associated hormones, somatostatin and gastrin-releasing peptide, and aspects of their interaction may be deregulated during progression to gastric adenocarcinoma. Furthermore, agonists and antagonists of the receptors for all three hormones have shown modest clinical efficacy against gastric adenocarcinoma, which might provide useful information on the future combined use of these agents.

摘要翻译： 

胃泌素是一种促增殖、抗凋亡的激素，在胃黏膜酸分泌中起核心作用，并在转基因小鼠模型中与恶性进展有长期关联。然而，其在人类胃恶性肿瘤中的确切作用仍需进一步验证。胃泌素的表达受两种密切相关激素——生长抑素和促胃泌素释放肽的严格调控，在进展为胃腺癌的过程中，它们之间的相互作用可能出现失调。此外，这三种激素受体的激动剂和拮抗剂在胃腺癌治疗中已显示出一定的临床疗效，这可能为未来联合应用这些药物提供有用信息。

原文链接：

Gastrin — active participant or bystander in gastric carcinogenesis?