title: Dickkopf-3 alters the morphological response to retinoic acid during neuronal differentiation of human embryonal carcinoma cells.
abstract: Dickkopf-3 (Dkk-3) and Dkkl-1 (Soggy) are secreted proteins of poorly understood function that are highly expressed in subsets of neurons in the brain. To explore their potential roles during neuronal development, we examined their expression in Ntera-2 (NT2) human embryonal carcinoma cells, which differentiate into neurons upon treatment with retinoic acid (RA). RA treatment increased the mRNA and protein levels of Dkk-3 but not of Dkkl-1. Ectopic expression of both Dkk-3 and Dkkl-1 induced apoptosis in NT2 cells. Gene silencing of Dkk-3 did not affect NT2 cell growth or differentiation but altered their response to RA in suspension cultures. RA treatment of NT2 cells cultured in suspension resulted in morphological changes that led to cell attachment and flattening out of cell aggregates. Although there were no significant differences in the expression levels of cell adhesion molecules in control and Dkk-3-silenced cells, this morphological response was not observed in Dkk-3-silenced cells. These findings suggest that Dkk-3 plays a role in the regulation of cell interactions during RA-induced neuronal differentiation.
authors.affiliation: Cell Biology and Stem Cells Unit, CIC bioGUNE, Spain.
authors.forename: Rocío Jiménez
authors.initials: RJ
authors.lastname: Alfonso
authors.forename: Irantzu
authors.initials: I
authors.lastname: Gorroño-Etxebarria
authors.forename: Miriam
authors.initials: M
authors.lastname: Rabano
authors.forename: Maria dM
authors.initials: Md
authors.lastname: Vivanco
authors.forename: Robert
authors.initials: R
authors.lastname: Kypta
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D018925:Chemokines; D054278:Embryonal Carcinoma Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D020868:Gene Silencing; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D050258:Mitosis Modulators / Q000494:pharmacology*; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; C498624:DKK3 protein, human; C577596:DKKL1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D050258:Mitosis Modulators; D012333:RNA, Messenger; D014212:Tretinoin; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7
keywords: NTera-2 cells; dickkopf-3; neuronal differentiation; retinoic acid