Transient modulation of cytoplasmic and nuclear retinoid receptors expression in differentiating human teratocarcinoma NT2 cells.
Human embryonal carcinoma Ntera2/D1 (NT2) cells treated with retinoic acid (RA) differentiate into several cell types including post-mitotic neurons. In this study we asked if RA-induced differentiation alters the expression of RA and retinol (ROL) binding proteins. The regulation of the intracellular carrier proteins for ROL and RA, cellular retinol binding protein I (CRBP-I), and cellular retinoic acid binding protein I and II (CRABP-I, CRABP-II) were studied along with the nuclear RA receptors RARalpha, RARbeta and RARgamma2. PCR analysis of total mRNA from RA-treated cells showed a biphasic early induction of CRBP-I, CRABP-II, and RARgamma2 genes. The immediate early gene Krox-24, a zinc finger transcription factor which is up-regulated during neuronal differentiation, was also induced, but after 1 week of treatment. The induction of CRBP-I protein synthesis in differentiating NT2 cells was confirmed by western blotting and immunofluorescence experiments. Conversely, the synthetic retinoid N-(4-hydroxyphenyl)retinamide, which induces cell death, but not differentiation in different tumour cell types, did not produce the same modulation on gene expression in NT2 cells. These data suggest that the RA-specific induction of CRBP-I and CRABP-II could be an early event in the process leading to neuronal differentiation of NT2 cells.
Borghi
Roberta
R
Laboratory of Molecular Biology, National Cancer Research Institute (IST), Genova, Italy.
Venè
Roberta
R
Arena
Giuseppe
G
Schubert
David
D
Albini
Adriana
A
Tosetti
Francesca
F
D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics; D051766:Early Growth Response Protein 1; D006801:Humans; D017874:Immediate-Early Proteins; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D012177:Retinol-Binding Proteins / Q000235:genetics / Q000378:metabolism; D054840:Retinol-Binding Proteins, Cellular; D018243:Teratocarcinoma / Q000378:metabolism* / Q000473:pathology*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics; D014407:Tumor Cells, Cultured; D000097768:Retinoic Acid Receptor gamma
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D012177:Retinol-Binding Proteins; D054840:Retinol-Binding Proteins, Cellular; D014157:Transcription Factors; D000097768:Retinoic Acid Receptor gamma; C497325:EGR1 protein, human; C518456:RBP1 protein, human; C082927:retinoic acid binding protein I, cellular; C082928:retinoic acid binding protein II, cellular