The transcription factor SNAIL represses vitamin D receptor expression and responsiveness in human colon cancer.
Several non-hypercalcemic analogs of 1alpha,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.
Pálmer
Héctor G
HG
Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, E-28029 Madrid, Spain.
Larriba
María Jesús
MJ
García
José Miguel
JM
Ordóñez-Morán
Paloma
P
Peña
Cristina
C
Peiró
Sandra
S
Puig
Isabel
I
Rodríguez
Rufo
R
de la Fuente
Ricardo
R
Bernad
Antonio
A
Pollán
Marina
M
Bonilla
Félix
F
Gamallo
Carlos
C
de Herreros
Antonio García
AG
Muñoz
Alberto
A
D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors; D015820:Cadherins / Q000378:metabolism; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors*; D003110:Colonic Neoplasms / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000494:pharmacology*
D000970:Antineoplastic Agents; D015820:Cadherins; D004268:DNA-Binding Proteins; D018167:Receptors, Calcitriol; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D002117:Calcitriol; C078903:seocalcitol