Decreased abundance of trefoil factor 1 transcript in the majority of gastric carcinomas
Decreased abundance of trefoil factor 1 transcript in the majority of gastric carcinomas
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DOI：
10.1002/cncr.11789
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发表时间：
2003-11-15
期刊：
影响因子：
6.2
通讯作者：
Powell, SM
中科院分区：
文献类型：
--
作者：
Beckler, AD;Roche, JK;Powell, SM
背景胃癌是世界范围内癌症相关死亡的主要原因之一，但其发生和进展的机制仍然很大程度上不确定。由于三叶因子1（TFF 1）表达的缺失导致小鼠胃窦粘膜肿瘤生长，作者试图全面研究原发性胃癌中的人TFF 1基因。作者通过DNA测序、实时定量逆转录-聚合酶链反应和酶联免疫吸附试验，在DNA、RNA和蛋白水平上研究了原发性胃癌和正常胃粘膜中的人TFF 1基因。值得注意的是，TFF 1 mRNA表达在所有37例胃癌研究与正常胃粘膜相比，显着下降。此外，六个肿瘤/正常对与可用的组织学样本显示在肿瘤样品中的蛋白质表达的显着降低。在一组42例人胃肿瘤中筛选整个TFF 1编码区没有发现任何体细胞突变，尽管发现了一些罕见的种系序列变异。这些发现证明了在大多数人胃癌中TFF 1转录物的显著减少，沿着蛋白表达的相应减少，这两者都发生在基因突变不存在的情况下。转录水平上TFF 1表达的失调是大多数胃癌发生发展的关键事件。(C)2003年美国癌症协会。
BACKGROUND. Gastric carcinoma is one of the leading causes of cancer-related death worldwide, but the mechanisms underlying its development and progression still remain largely uncharacterized. As loss of trefoil factor 1 (TFF1) expression leads to neoplastic growth in the antropyloric mucosa of mice, the authors sought to comprehensively study the human TFF1 gene in primary gastric carcinomas.METHODS. The authors Studied the human TFF1 gene in primary gastric carcinomas and normal gastric mucosa at the DNA, RNA, and protein levels through DNA sequencing, quantitative real-time reverse transcriptase-polymerase chain reaction, and immunohistochemistry.RESULTS. Strikingly, TFF1 mRNA expression was significantly decreased in all 37 gastric carcinomas studied compared with normal gastric mucosa. Furthermore, six tumor/normal pairs with available histologic samples demonstrated a marked decrease in protein expression in tumor samples. Screening of the entire TFF1 coding region in a panel of 42 human gastric tumors did not reveal any somatic mutations, although a few rare germline sequence variants were identified.CONCLUSIONS. These findings demonstrated a significant decrease in the TFF1 transcript in the majority of human gastric carcinomas along with a corresponding reduction in protein expression, both of which occurred in the absence of gene Mutation. Dysregulation of TFF1 expression at the transcript level was a critical event in the development of most gastric carcinomas. (C) 2003 American Cancer Society.