Transient modulation of cytoplasmic and nuclear retinoid receptors expression in differentiating human teratocarcinoma NT2 cells

Roberta Borghi, Roberta Venè, Giuseppe Arena, David Schubert, Adriana Albini, Francesca Tosetti

Research output: Contribution to journalArticlepeer-review

Abstract

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 RARα, RARβ and RARγ2. PCR analysis of total mRNA from RA-treated cells showed a biphasic early induction of CRBP-I, CRABP-II, and RARγ2 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.

Original languageEnglish
Pages (from-to)94-104
Number of pages11
JournalJournal of Neurochemistry
Volume84
Issue number1
DOIs
Publication statusPublished - Jan 2003

Keywords

  • 4HPR
  • Neuronal differentiation
  • Ntera2/D1
  • Retinoic acid
  • Retinoid binding proteins
  • Teratocarcinoma

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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