Human Molecular Genetics Advance Access originally published online on October 3, 2005
Human Molecular Genetics 2005 14(22):3361-3370; doi:10.1093/hmg/ddi366
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E-cadherin and vitamin D receptor regulation by SNAIL and ZEB1 in colon cancer: clinicopathological correlations
1Department of Medical Oncology, 2Department of Surgery, 3Biostatistics Unit and 4Department of Pathology, Hospital Universitario Puerta de Hierro, Madrid, Spain, 5Department of Pathology, Hospital Virgen de la Salud, Toledo, Spain, Hospital Universitario Puerta de Hierro, Madrid, Spain, 6Unitat de Biología Cellular i Molecular, Institut Municipal d'Investigació Mèdica-Universitat Pompeu-Fabra, Barcelona, Spain and 7Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Spain
* To whom correspondence should be addressed at: Department of Medical Oncology, Hospital Universitario Puerta de Hierro, C/ San Martín de Porres, 4, 28035 Madrid, Spain. Email: felixbv{at}stnet.es
Received September 8, 2005; Accepted September 23, 2005
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.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.
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