Farook V S, Alkhalaf M, Karam S M
Department of Anatomy, Faculty of Medicine, Kuwait University, Safat, Kuwait.
Cell Prolif. 2008 Apr;41(2):310-20. doi: 10.1111/j.1365-2184.2008.00522.x.
In this study the gastric mucosa of transgenic mice expressing the simian virus 40 large T antigen gene in the parietal cell lineage is used to establish and characterize a new epithelial progenitor cell line. In these mice, proliferation and amplification of preparietal cells preclude their maturation into acid-secreting parietal cells leading to achlorohydria, hyperplasia, dysplasia and eventually gastric adenocarcinoma.
Enzymatically dispersed gastric epithelial cells were cultured, cloned and screened using immunohistochemical methods, for expression of a variety of biomarkers of differentiated pit, parietal, enteroendocrine and neck/zymogenic cells.
A biomarker-deficient cell line whose ultrastructural features resembled those of mouse gastric epithelial progenitor cells was established. Treatment with either hydrocortisone or oestrogen significantly enhanced proliferation of these cells, whereas retinoic acid inhibited their growth. No change in differentiation was detected with any of these treatments; however, when these cells were injected subcutaneously into nude mice, they proliferated to form tumours and undergo partial differentiation towards parietal cell lineage.
This mouse gastric epithelial progenitor cell line could be useful as an in vitro model to study growth properties, proliferation and differentiation of a subpopulation of gastric epithelial progenitor cells and also to study gastric carcinogenesis.
在本研究中，利用在壁细胞谱系中表达猿猴病毒40大T抗原基因的转基因小鼠的胃黏膜来建立并鉴定一种新的上皮祖细胞系。在这些小鼠中，壁前体细胞的增殖和扩增阻止了它们成熟为分泌酸的壁细胞，导致胃酸缺乏、增生、发育异常并最终发展为胃腺癌。
对酶解分散的胃上皮细胞进行培养、克隆，并采用免疫组织化学方法筛选分化的胃小凹、壁、肠内分泌和颈部/泌酸细胞的多种生物标志物的表达情况。
建立了一种生物标志物缺陷的细胞系，其超微结构特征与小鼠胃上皮祖细胞相似。用氢化可的松或雌激素处理可显著增强这些细胞的增殖，而视黄酸则抑制其生长。这些处理均未检测到分化的变化；然而，当将这些细胞皮下注射到裸鼠体内时，它们会增殖形成肿瘤并向壁细胞谱系进行部分分化。
这种小鼠胃上皮祖细胞系可作为体外模型，用于研究胃上皮祖细胞亚群的生长特性、增殖和分化，也可用于研究胃癌发生。
