Spasmolytic polypeptide expressing metaplasia to preneoplasia in H-felis-infected mice
Spasmolytic polypeptide expressing metaplasia to preneoplasia in H-felis-infected mice
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DOI：
10.1053/j.gastro.2004.05.029
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发表时间：
2004-08-01
期刊：
影响因子：
29.4
通讯作者：
Goldenring, JR
中科院分区：
文献类型：
--
作者：
Nomura, S;Baxter, T;Goldenring, JR
背景与目的：慢性幽门螺杆菌感染引起的氧合性萎缩和化生细胞系的出现易导致胃肿瘤的发生。我们描述了一个三叶因子家族2 （TFF2；痉挛性多肽）表达化生（SPEM）与胃肿瘤在啮齿类动物和人类眼底。为了研究spm与猫狸猴感染的C57BL/6小鼠肿瘤过程的关系，我们现在研究了SPEW相关转录物与瘤前病变的关系。方法：通过基因芯片分析spw的相关转录本，并通过激光捕获显微解剖分离感染6个月的雄性C57BL/6小鼠同一胃切片的表面黏液细胞。通过原位杂交和定量RT-PCR以及免疫组织化学检测胸腺蛋白酶α的表达来评估spem相关转录物的表达。结果：鉴定出11个SPEW相关转录本仅在SPEM中可检测到。通过原位杂交和定量PCR验证了spem相关转录本的表达。一种转录物，即非编码RNA Xist，仅在受感染雄性小鼠的SPEM细胞中被鉴定出来。11个转录本中的10个以及TFF2也在深囊性胃炎区域表达。其中一种鉴定的蛋白原胸腺酶α的免疫细胞化学显示，在SPEM和深囊性胃炎中有明显的核染色。结论：深囊性胃炎区域spm相关转录本的表达表明，SPEM代表了胃癌动物模型中发育不良的前体谱系。
Background & Aims: The emergence of oxyntic atrophy and metaplastic cell lineages in response to chronic Helicobacter pylori infection predisposes to gastric neoplasia. We have described a trefoil factor family 2 (TFF2; spasmolytic polypeptide) expressing metaplasia (SPEM) associated with gastric neoplasia in both rodent and human fundus. To examine the relationship of SPEM to the neoplastic process in the H. felis-infected C57BL/6 mouse, we have now studied the association of SPEW related transcripts with preneoplasia.Methods: SPEW related transcripts were identified by microarray analysis of amplified cRNA from SPEM, and surface mucous cells were isolated by laser capture microdissection from the same gastric sections from male C57BL/6 mice infected with H. felis for 6 months. Expression of SPEM-related transcripts was assessed by in situ hybridization and quantitative RT-PCR, as well as immunohistochemistry for prothymosin alpha.Results: Eleven SPEW related transcripts were identified as detectable only in SPEM. The expression of the SPEM-related transcripts was validated by in situ hybridization and quantitative PCR. One transcript, the noncoding RNA Xist, was only identified in SPEM cells from the infected male mice. Ten of the 11 transcripts as well as TFF2 were also expressed in regions of gastritis cystica profunda. lmmunocytochemistry for one of the identified proteins, prothymosin alpha, demonstrated prominent nuclear staining in SPEM and gastritis cystica profunda.Conclusions: The expression of SPEM-related transcripts in regions of gastritis cystica profunda suggests that SPEM represents a precursor lineage for the development of dysplasia in this animal model of gastric carcinogenesis.