Beckler Andrew D, Roche James K, Harper Jeffrey C, Petroni Gina, Frierson Henry F, Moskaluk Christopher A, El-Rifai Wa'el, Powell Steven M
Department of Medicine, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
Cancer. 2003 Nov 15;98(10):2184-91. doi: 10.1002/cncr.11789.
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.
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.
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.
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.
胃癌是全球癌症相关死亡的主要原因之一，但其发生和发展的机制仍大多未明确。由于三叶因子1（TFF1）表达缺失会导致小鼠胃幽门黏膜发生肿瘤性生长，作者试图全面研究原发性胃癌中的人类TFF1基因。
作者通过DNA测序、定量实时逆转录聚合酶链反应和免疫组织化学，在DNA、RNA和蛋白质水平研究原发性胃癌和正常胃黏膜中的人类TFF1基因。
令人惊讶的是，与正常胃黏膜相比，在研究的所有37例胃癌中TFF1 mRNA表达均显著降低。此外，6对有可用组织学样本的肿瘤/正常组织对显示肿瘤样本中蛋白质表达明显降低。在一组42例人类胃肿瘤中筛查整个TFF1编码区未发现任何体细胞突变，尽管鉴定出了一些罕见的种系序列变异。
这些发现表明，大多数人类胃癌中TFF1转录本显著减少，同时蛋白质表达相应降低，且两者均在无基因突变的情况下发生。TFF1表达在转录水平的失调是大多数胃癌发生过程中的关键事件。
