Human Molecular Genetics Advance Access published online on October 3, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi366
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1 Department of Medical Oncology, Hospital Universitario Puerta de Hierro, Madrid, Spain
* To whom correspondence should be addressed. E-cadherin gene (CDH1) expression is strictly regulated. The transcriptional factors SNAIL and ZEB1 are involved in its repression, while activation of vitamin D receptor (VDR) by vitamin D induces its transcription. We study the expression and functional correlation of these four genes and examine their possible involvement in colon cancer. The expression of SNAIL, CDH1, VDR and ZEB1 genes was measured by RT-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 expression. 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 analogues.
Received September 8, 2005
Accepted September 23, 2005
Article
E-cadherin and Vitamin D Receptor Regulation by SNAIL and ZEB1 in Colon Cancer. Clinicopathological correlations
2 Department of Pathology, Hospital Virgen de la Salud, Toledo, Spain
3 Department of Surgery, Hospital Universitario Puerta de Hierro, Madrid, Spain
4 Biostatistics Unit, Hospital Universitario Puerta de Hierro, Madrid, Spain
5 Department of Pathology, Hospital Universitario Puerta de Hierro, Madrid, Spain
6 Unitat de Biología Cellular i Molecular, Institut Municipal d'Investigació Mèdica-Universitat Pompeu-Fabra, Barcelona, Spain
7 Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Spain
8 Department of Medical Oncology, Hospital Universitario Puerta de Hierro, C/ San Martín de Porres, 4, 28035-Madrid, Spain
Félix Bonilla, E-mail: felixbv{at}stnet.es
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