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SNAI1 expression in colon cancer related with CDH1 and VDR downregulation in normal adjacent tissue

Oncogene volume 28, pages 4375–4385 (2009)Cite this article

Abstract

SNAI1, ZEB1, E-cadherin (CDH1), and vitamin D receptor (VDR) genes regulate the epithelial–mesenchymal transition (EMT) that initiates the invasion process of many tumor cells. We hypothesized that this process could also affect the behavior of normal cells adjacent to the tumor. To verify this hypothesis, the expression level of these genes was determined by quantitative RT–PCR in tumor, normal adjacent, and normal distant tissues from 32 colorectal cancer (CC) patients. In addition, we extended the study to human HaCaT normal keratinocytes and SW480-ADH colon cancer cells co-cultured with SW480-ADH cells overexpressing the mouse Snai1 gene. Of 18 CC cases with SNAI1 expression in tumor tissue, five also had SNAI1 in normal adjacent tissue (NAT). Expression of SNAI1 in tumor tissue correlated with downregulation of CDH1 and VDR genes in both tumor (P=0.047 and P=0.014, respectively) and NAT lacking SNAI1 expression (P=0.054 and P=0.003). ZEB1 expression was directly related to VDR expression in tumor tissue (r=0.39; P=0.027) and inversely to CDH1 in NAT (r=−0.46; P=0.010). CDH1 and VDR were also downregulated in SW480-ADH and MaCaT cells, respectively, when they were co-cultured with Snai1-expressing cells. Furthermore, cytokine analysis showed differences in the conditioned media obtained from the two cell types. These results indicate that histologically normal tissue adjacent to tumor tissue expressing the EMT-inducing gene SNAI1 shows alterations in the expression of epithelial differentiation genes such as CDH1 and VDR.

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Abbreviations

AI:

allele imbalance

CC:

colorectal cancer

EMT:

epithelial–mesenchymal transition

LOH:

loss of heterozygosity

N:

normal

NAT:

normal adjacent tissue

T:

tumor

VDR:

vitamin D receptor

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Acknowledgements

We thank M Eaude for help with the English paper. This study was supported by the grants SAF2007-60431, CAM: S-GEN/0266/2006, ISCIII-RETIC RD06/0020 and /0009, and a grant from the Accion Transversal del Cancer (ISCIII).

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Author notes

  1. C Peña and J M García: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Oncology, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Madrid, Spain

    C Peña, J M García, I Gómez, M Herrera, V García, J Silva, G Domínguez & F Bonilla

  2. Instituto de Investigaciones Biomédicas ‘Alberto Sols’, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain

    M J Larriba & A Muñoz

  3. Functional Proteomics Laboratory, Centro de Investigaciones Biológicas (CIB-CSIC), Madrid, Spain

    R Barderas & J I Casal

  4. Department of Pathology, Hospital Virgen de la Salud, Toledo, Spain

    R Rodríguez

  5. Department of Pathology, Hospital General Universitario, Guadalajara, Spain

    J Cuevas

  6. Unitat de Biología Cellular i Molecular, Institut Municipal d'Investigació Mèdica, Universitat Pompeu Fabra, Barcelona, Spain

    A G de Herreros

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Correspondence to F Bonilla.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Peña, C., García, J., Larriba, M. et al. SNAI1 expression in colon cancer related with CDH1 and VDR downregulation in normal adjacent tissue. Oncogene 28, 4375–4385 (2009). https://doi.org/10.1038/onc.2009.285

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