Differential expression of the epithelial-mesenchymal transition regulators snail, SIP1, and twist in gastric cancer
Differential expression of the epithelial-mesenchymal transition regulators snail, SIP1, and twist in gastric cancer
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DOI：
10.1016/s0002-9440(10)64464-1
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发表时间：
2002-11-01
影响因子：
6
通讯作者：
Becker, KF
中科院分区：
文献类型：
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作者：
Rosivatz, E;Becker, I;Becker, KF
上皮-间质转化（Epithelial-mesenchymal transition， EMT）涉及E-cadherin的下调，被认为在癌细胞侵袭和转移的早期阶段发挥了重要作用。我们的研究目的是阐明EMT调节因子Snail， SIPI（两者都是E-cadherin的直接抑制因子）和Twist（果蝇胚胎发生过程中N-cadherin的激活因子）在原发性人胃癌中的作用。采用实时定量RT-PCR方法分析48例胃癌组织中石蜡包埋和福尔马林固定组织中Snail、SIP1和Twist的表达情况。与匹配的非肿瘤组织相比，这些基因在恶性组织中的表达水平变化与E-和N-cadherin的表达相关。在28例弥漫性胃癌中，与非肿瘤组织相比，11例（39%）检测到E-cadherin表达降低。在6例E-cadherin表达降低或阴性的病例中，Snail表达上调。然而，与SIPI表达增加无关。有趣的是，我们在6例中检测到N-cadherin mRNA的异常表达，其中4例与Twist过表达相关。在20例肠型胃癌样本中，有12例（60%）E-cadherin表达降低，这与SIP1表达上调有关，因为这12例中有10例出现mRNA水平升高，而Snail、Twist和N-cadherin没有上调。我们首次研究了EMT调节因子在人类胃癌中的作用，并提供了证据表明，在弥漫性胃癌中，Snail mRNA表达的增加与E-cadherin的下调有关。我们在相同的肿瘤中检测到N-cadherin mRNA水平异常阳性或升高，可能是由于Twist的过度表达。SIPI过表达与E-cadherin在弥漫性肿瘤中的下调无关，但被发现参与肠型胃癌的发病。我们得出结论，EMT调节因子在胃癌发生中发挥不同的作用，取决于组织学亚型。
Epithelial-mesenchymal transition (EMT) involving down-regulation of E-cadherin is thought to play a fundamental role during early steps of invasion and metastasis of carcinoma cells. The aim of our study was to elucidate the role of EMT regulators Snail, SIPI (both are direct repressors of E-cadherin), and Twist (an activator of N-cadherin during Drosophild embryogenesis), in primary human gastric cancers. Expression of Snail, SIP1, and Twist was analyzed in 48 gastric carcinomas by real-time quantitative RT-PCR in paraffin-embedded and formalin-fixed tissues. The changes of expression levels of these genes in malignant tissues compared to matched non-tumorous tissues were correlated with the expression of E- and N-cadherin. From 28 diffuse-type gastric carcinomas analyzed reduced E-cadherin expression was detected in 11 (39%) cases compared to non-tumorous tissues. Up-regulated Snail could be found in 6 cases with reduced or negative E-cadherin expression. However, there was no correlation to increased SIPI expression. Interestingly, we could detect abnormal expression of N-cadherin mRNA in 6 cases, which was correlated with Twist overexpression in 4 cases. From 20 intestinal-type gastric cancer samples reduced E-cadherin expression was found in 12 (60%) cases, which was correlated to up-regulation of SIP1, since 10 of these 12 cases showed elevated mRNA levels, whereas Snail, Twist, and N-cadherin were not up-regulated. We present the first study investigating the role of EMT regulators in human gastric cancer and provide evidence that an increase in Snail mRNA expression is associated with down-regulation of E-cadherin in diffuse-type gastric cancer. We detected abnormally positive or increased N-cadherin mRNA levels in the same tumors, probably due to overexpression of Twist. SIPI overexpression could not be linked to down-regulated E-cadherin in diffuse-type tumors, but was found to be involved in the pathogenesis of intestinal-type gastric carcinoma. We conclude that, EMT regulators play different roles in gastric carcinogenesis depending on the histological subtype.