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

Several non-hypercalcemic analogs of 1α,25-dihydroxyvitamin D3 (1,25(OH) 2 D 3 ) 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...

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Veröffentlicht in:	Nature medicine 2004-09, Vol.10 (9), p.917-919
Hauptverfasser:	Pálmer, Héctor G, Larriba, María Jesús, García, José Miguel, Ordóñez-Morán, Paloma, Peña, Cristina, Peiró, Sandra, Puig, Isabel, Rodríguez, Rufo, de la Fuente, Ricardo, Bernad, Antonio, Pollán, Marina, Bonilla, Félix, Gamallo, Carlos, de Herreros, Antonio García, Muñoz, Alberto
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Antineoplastic Agents - antagonists & inhibitors Biomedical and Life Sciences Biomedicine brief-communication Cadherins - metabolism Calcitriol - analogs & derivatives Calcitriol - antagonists & inhibitors Cancer Research Colonic Neoplasms - metabolism DNA-Binding Proteins - pharmacology Dose-Response Relationship, Drug Electrophoretic Mobility Shift Assay Gene Expression Regulation, Neoplastic - drug effects Humans Immunoprecipitation Infectious Diseases Metabolic Diseases Mice Molecular Medicine Neurosciences Promoter Regions, Genetic - genetics Receptors, Calcitriol - genetics Receptors, Calcitriol - metabolism Snail Family Transcription Factors Transcription Factors - pharmacology Vitamin D
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Zusammenfassung:	Several non-hypercalcemic analogs of 1α,25-dihydroxyvitamin D3 (1,25(OH) 2 D 3 ) 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) 2 D 3 analog, in xenografted mice. In human colon cancers, elevated SNAIL expression correlates with downregulation of VDR .
ISSN:	1078-8956 1546-170X
DOI:	10.1038/nm1095