CDH1 POLYMORPHISMS AND LOW EXPRESSION OF E-CADHERIN AND β-CATENIN IN COLORECTAL CANCER PATIENTS.
Epithelial-mesenchymal transition (EMT) process has a central role in tumor progression and metastases. Loss of cell-to-cell adhesiveness is a key step in EMT. In particular, E-cadherin and β-catenin, components of the adherens junctions, play a strategic role. Accumulation of β-catenin at cytoplasmic level following adherens junctions disruption, induces its translocation into the nucleus, where it binds to members of the TCF/LEF family of transcription factors. In particular, Lymphoid Enhancer-Binding factor 1 (LEF1) product can target genes involved in EMT. The aim of the present study was to evaluate the influence of CDH1 and CTNNB1 genes, coding for E-cadherin and β-catenin respectively and LEF1 in a sample study of 140 Italian patients affected by colorectal cancer. An association study between four single nucleotide polymorphisms (rs11865026, rs11642413, rs13689, and rs10431923) of CDH1 and the disease did not provide statistically significant results. The gene expression analysis carried out for CDH1, CTNNB1 and LEF1 in 54 paired specimens from 27 patients provided evidence of a reduced expression of the first two in cancer tissues. We believe there may be a sort of cross regulation between the products of these two genes which closely interact in EMT activation and that such hypothesis should be further investigated in a greater number of cases.
Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy; Centre of Molecular Genetics, CARISBO Foundation, University of Bologna, Bologna, Italy.
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Martinelli
Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy; Centre of Molecular Genetics, CARISBO Foundation, University of Bologna, Bologna, Italy.
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Palmieri
Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy; Centre of Molecular Genetics, CARISBO Foundation, University of Bologna, Bologna, Italy.
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Rodia
Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
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Cura
Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy; Centre of Molecular Genetics, CARISBO Foundation, University of Bologna, Bologna, Italy.
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Scapoli
Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
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Ugolini
Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
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Montroni
Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy; Centre of Molecular Genetics, CARISBO Foundation, University of Bologna, Bologna, Italy.
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De Sanctis
Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy; Centre of Molecular Genetics, CARISBO Foundation, University of Bologna, Bologna, Italy.
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Solmi