E-cadherin and vitamin D receptor regulation by SNAIL and ZEB1 in colon cancer:: clinicopathological correlations
E-cadherin and vitamin D receptor regulation by SNAIL and ZEB1 in colon cancer:: clinicopathological correlations
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DOI：
10.1093/hmg/ddi366
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发表时间：
2005-11-15
影响因子：
3.5
通讯作者：
Bonilla, F
中科院分区：
文献类型：
--
作者：
Peña, C;García, JM;Bonilla, F
E-cadherin（CDH 1）基因表达受到严格调控。转录因子SNAIL和ZEB 1参与其抑制，而维生素D受体（VDR）的激活诱导其转录。我们研究了SNAIL，CDH 1，VDR和ZEB 1基因的表达和功能相关性，并检查它们在结肠癌中的可能参与。采用真实的时间PCR方法检测114例大肠癌组织中这4个基因的表达，并分析其肿瘤特征。SNAIL表达与CDH 1（P < 0.001）和VDR（P < 0.001）基因产物的下调有关。我们还发现CDH 1和VDR表达之间呈正相关。然而，在ZEB 1高表达的患者中，未发现SNAIL与CDH 1之间的关联。我们观察到以下下调之间的相关性：a）ZEB 1和手术切除中息肉的存在; B）VDR和低分化; c）CDH 1和低分化、血管浸润、淋巴结转移和晚期的存在;以及肿瘤中SNAIL表达和血管浸润之间的相关性趋势。SNAIL、CDH 1、VDR和ZEB 1之间的相关性以及CDH 1和VDR表达减少与侵袭性肿瘤特征之间的关联强调了分析结肠癌患者中这些基因用于预后目的和用于预测对维生素D或其类似物的可能疗法的响应的价值。
E-cadherin (CDH1) gene expression is strictly regulated. The transcriptional factors SNAIL and ZEB1 are involved in its repression, whereas activation of vitamin D receptor (VDR) by vitamin D induces its transcription. We study the expression and functional correlation of SNAIL, CDH1, VDR and ZEB1 genes and examine their possible involvement in colon cancer. The expression of these four genes was measured by real time-PCR in 114 patients with colorectal cancer, and tumor characteristics were analyzed in each patient. SNAIL expression was associated with downregulation of CDH1 (P < 0.001) and VDR (P < 0.001) gene products. We also found a positive correlation between CDH1 and VDR expressions. However, the association between SNAIL and CDH1 was not found in patients with high expression of ZEB1. We observed a correlation between downregulation of: a) ZEB1 and presence of polyps in surgical resections; b) VDR and poor differentiation and c) CDH1 and poor differentiation, vascular invasion, presence of lymph node metastases and advanced stages; as well as a trend toward a correlation between SNAIL expression in tumors and vascular invasion. The correlations between SNAIL, CDH1, VDR and ZEB1 and the association between reduced expression of CDH1 and VDR and aggressive tumor characteristics emphasize the value of analyzing these genes in colon cancer patients for prognostic purposes and for predicting response to possible therapies with vitamin D or its analogs.