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

Nature Medicine volume 10, pages 917–919 (2004)Cite this article

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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Figure 1: SNAIL inhibits VDR expression and function in human SW480-ADH cells.
Figure 2: High SNAIL expression inhibits EB1089 antitumor action in vivo and correlates with VDR downregulation in human colon tumors.

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References

  1. Hansen, C.M., Binderup, L., Hamberg, K.J. & Carlberg, C. Front. Biosci. 6, D820–D848 (2001).

    CAS  PubMed  Google Scholar 

  2. Lamprecht, S.A. & Lipkin, M. Nat. Rev. Cancer 3, 601–614 (2003).

    Article  CAS  Google Scholar 

  3. Dalhoff, K. et al. Br. J. Cancer 89, 252–257 (2003).

    Article  CAS  Google Scholar 

  4. Kállay, E. et al. Food Chem. Toxicol. 40, 1191–1196 (2002).

    Article  Google Scholar 

  5. Jurutka, P.W. et al. Rev. Endocr. Metab. Disord. 2, 203–216 (2001).

    Article  CAS  Google Scholar 

  6. Cross, H.S. et al. Anticancer Res. 16, 2333–2338 (1996).

    CAS  PubMed  Google Scholar 

  7. Pálmer, H.G. et al. J. Cell Biol. 154, 369–388 (2001).

    Article  Google Scholar 

  8. Cano, A. et al. Nat. Cell Biol. 2, 76–83 (2000).

    Article  CAS  Google Scholar 

  9. Batlle, E. et al. Nat. Cell Biol. 2, 84–89 (2000).

    Article  CAS  Google Scholar 

  10. Nieto, M.A. Nat. Rev. Mol. Cell Biol. 3, 155–166 (2002).

    Article  CAS  Google Scholar 

  11. Pálmer, H.G. et al. Cancer Res. 63, 7799–7806 (2003).

    PubMed  Google Scholar 

  12. Van de Wetering, M. et al. Cell 111, 241–250 (2002).

    Article  CAS  Google Scholar 

  13. Zinser, G.M., Sundberg, J.P. & Welsh, J. Carcinogenesis 23, 2103–2109 (2002).

    Article  CAS  Google Scholar 

  14. Makishima, M. et al. Science 296, 1313–1316 (2002).

    Article  CAS  Google Scholar 

  15. Huerta, S. et al. Cancer Res. 62, 741–746 (2002).

    CAS  PubMed  Google Scholar 

Download references

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.

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Author notes

  1. Héctor G Pálmer and María Jesús Larriba: These authors contributed equally to this work.

Authors and Affiliations

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

    Héctor G Pálmer, María Jesús Larriba, Paloma Ordóñez-Morán & Alberto Muñoz

  2. Hospital Universitario Puerta de Hierro, Madrid, E-28035, Spain

    José Miguel García, Cristina Peña & Félix Bonilla

  3. Institut Municipal d'Investigació Mèdica–Universitat Pompeu-Fabra, Barcelona, E-08003, Spain

    Sandra Peiró, Isabel Puig & Antonio García de Herreros

  4. Hospital Virgen de la Salud, Toledo, E-45004, Spain

    Rufo Rodríguez

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

    Ricardo de la Fuente & Antonio Bernad

  6. Centro Nacional de Epidemiología, Madrid, E-28029, Spain

    Marina Pollán

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

    Carlos Gamallo

Authors
  1. Héctor G Pálmer
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  2. María Jesús Larriba
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  15. Alberto Muñoz
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Corresponding author

Correspondence to Alberto Muñoz.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Sequence of the human VDR gene promoter. (PDF 102 kb)

Supplementary Fig. 2

Specificity of the repressive effective of SNAIL on human VDR gene promoter. (PDF 162 kb)

Supplementary Fig. 3

High SNAIL levels associate with E-cadherin repression in human colon cancer. (PDF 139 kb)

Supplementary Table 1

Inverse correlation between SNAIL and VDR expression in colon cancer. (PDF 179 kb)

Supplementary Table 2

Statistical analysis of the inverse relation between tumoral SNAIL RNA overexpression and the repression of VDR and E-cadherin expression. (PDF 85 kb)

Supplementary Methods (PDF 45 kb)

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Pálmer, H., Larriba, M., García, J. et al. The transcription factor SNAIL represses vitamin D receptor expression and responsiveness in human colon cancer. Nat Med 10, 917–919 (2004). https://doi.org/10.1038/nm1095

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