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The transcription factor SNAIL represses vitamin D receptor expression and responsiveness in human colon cancer

Nature Medicine volume 10, pages 917919 (2004) | Download Citation

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Abstract

Several non-hypercalcemic analogs of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) show antitumor activity in a subset of cancer patients. High vitamin D receptor (VDR) expression, which is associated with good prognosis but is lost during tumor progression. We show that the SNAIL transcription factor represses VDR gene expression in human colon cancer cells and blocks the antitumor action of EB1089, a 1,25(OH)2D3 analog, in xenografted mice. In human colon cancers, elevated SNAIL expression correlates with downregulation of VDR.

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Acknowledgements

We thank L. Binderup for 1,25(OH)2D3 and EB1089, T. González for calcemia measurement and R. Rycroft for his help with the English manuscript. This study was supported by grants from Fundación Científica de la Asociación Española contra el Cáncer, Ministerio de Ciencia y Tecnología (SAF01-2291) and Instituto de Salud Carlos III (FIS03-C03/10) of Spain.

Author information

Author notes

    • Héctor G Pálmer
    •  & María Jesús Larriba

    These authors contributed equally to this work.

Affiliations

  1. Instituto de Investigaciones Biomédicas “Alberto Sols,” Consejo Superior de Investigaciones Científicas–Universidad Autónoma de Madrid, E-28029 Madrid, Spain.

    • Héctor G Pálmer
    • , María Jesús Larriba
    • , Paloma Ordóñez-Morán
    •  & Alberto Muñoz
  2. Hospital Universitario Puerta de Hierro, E-28035 Madrid, Spain.

    • José Miguel García
    • , Cristina Peña
    •  & Félix Bonilla
  3. Institut Municipal d'Investigació Mèdica–Universitat Pompeu-Fabra, E-08003 Barcelona, Spain.

    • Sandra Peiró
    • , Isabel Puig
    •  & Antonio García de Herreros
  4. Hospital Virgen de la Salud, E-45004 Toledo, Spain.

    • Rufo Rodríguez
  5. Centro Nacional de Biotecnología, E-28049 Madrid, Spain.

    • Ricardo de la Fuente
    •  & Antonio Bernad
  6. Centro Nacional de Epidemiología, E-28029 Madrid, Spain.

    • Marina Pollán
  7. Hospital Universitario de la Princesa, E-28006 Madrid, Spain.

    • Carlos Gamallo

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Alberto Muñoz.

Supplementary information

PDF files

  1. 1.

    Supplementary Fig. 1

    Sequence of the human VDR gene promoter.

  2. 2.

    Supplementary Fig. 2

    Specificity of the repressive effective of SNAIL on human VDR gene promoter.

  3. 3.

    Supplementary Fig. 3

    High SNAIL levels associate with E-cadherin repression in human colon cancer.

  4. 4.

    Supplementary Table 1

    Inverse correlation between SNAIL and VDR expression in colon cancer.

  5. 5.

    Supplementary Table 2

    Statistical analysis of the inverse relation between tumoral SNAIL RNA overexpression and the repression of VDR and E-cadherin expression.

  6. 6.

    Supplementary Methods

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DOI

https://doi.org/10.1038/nm1095