Liu Wei, Pan Hua-Feng, Wang Qi, Zhao Zi-Ming
Institute of Gastroenterology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.
Institute of Gastroenterology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.
Pathol Res Pract. 2018 Dec;214(12):1929-1939. doi: 10.1016/j.prp.2018.10.022. Epub 2018 Oct 23.
Gastric intestinal metaplasia is a precursor for gastric dysplasia, which is in turn, a risk factor for gastric adenocarcinoma. Gastric metaplasia and dysplasia are known as gastric precancerous lesions (GPLs), which are essential stages in the progression from normal gastric mucosa to gastric cancer (GC) or gastric adenocarcinoma. Genetically-engineered mice have become essential tools in various aspects of GC research, including mechanistic studies and drug discovery. Studies in mouse models have contributed significantly to our understanding of the pathogenesis and molecular mechanisms underlying GPLs and GC. With the development and improvement of gene transfer technology, investigators have created a variety of transgenic and gene knockout mouse models for GPLs, such as H/K-ATPase transgenic and knockout mutant mice and gastrin gene knockout mice. Combined with Helicobacter infection, and treatment with chemical carcinogens, these mice develop GPLs or GC and thus provide models for studying the molecular biology of GC, which may lead to the discovery and development of novel drugs. In this review, we discuss recent progress in the use of genetically-engineered mouse models for GPL research, with particular emphasis on the importance of examining the gastric mucosa at the histological level to investigate morphological changes of GPL and GC and associated protein and gene expression.
胃肠化生是胃发育异常的前驱病变，而胃发育异常又是胃腺癌的一个危险因素。胃化生和发育异常被称为胃癌前病变（GPLs），是从正常胃黏膜发展到胃癌（GC）或胃腺癌的关键阶段。基因工程小鼠已成为GC研究各个方面的重要工具，包括机制研究和药物发现。小鼠模型研究对我们理解GPLs和GC的发病机制及分子机制做出了重大贡献。随着基因转移技术的发展和改进，研究人员创建了多种用于GPLs的转基因和基因敲除小鼠模型，如H/K-ATP酶转基因和敲除突变小鼠以及胃泌素基因敲除小鼠。结合幽门螺杆菌感染以及化学致癌物处理，这些小鼠会发生GPLs或GC，从而为研究GC的分子生物学提供模型，这可能会带来新药的发现和开发。在本综述中，我们讨论了基因工程小鼠模型用于GPL研究的最新进展，特别强调在组织学水平检查胃黏膜以研究GPL和GC的形态变化以及相关蛋白质和基因表达的重要性。
