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.
Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, E-28029 Madrid, Spain.
Héctor G
HG
Pálmer
María Jesús
MJ
Larriba
José Miguel
JM
García
Paloma
P
Ordóñez-Morán
Cristina
C
Peña
Sandra
S
Peiró
Isabel
I
Puig
Rufo
R
Rodríguez
Ricardo
R
de la Fuente
Antonio
A
Bernad
Marina
M
Pollán
Félix
F
Bonilla
Carlos
C
Gamallo
Antonio García
AG
de Herreros
Alberto
A
Muñoz
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