Retinoic acid stimulates the protein kinase C pathway before activation of its β-nuclear receptor during human teratocarcinoma differentiation Journal Article


Authors: Kurie, J. M.; Younes, A.; Miller, W. H. Jr; Burchert, M.; Chiu, C. F.; Kolesnick, R.; Dmitrovsky, E.
Article Title: Retinoic acid stimulates the protein kinase C pathway before activation of its β-nuclear receptor during human teratocarcinoma differentiation
Abstract: We previously reported that protein kinase C (PKC) stimulation through phorbol ester (TPA) treatment enhances the effects of all-trans retinoic acid (RA) on immunophenotypic differentiation and RA nuclear receptor (RAR) activation in the multipotential human teratocarcinoma (TC) cell line NTera-2 clone D1 (abbreviated NT2 D1). This study extends prior work in NT2 D1 cells by demonstrating that PKC pathway activation is an early effect of RA treatment which regulates RAR transcriptional activity. RA activated the PKC pathway prior to induction of RAR-β expression at 6 h, which is an established early marker of RAR activation in NT2 D1 cells. RA caused a transient 1.3-fold increase in intracellular diacylglycerol (DG) at 2 min and a translocation of the gamma isozyme of PKC (PKC-γ) within 5 min. Transient co-transfection studies provided evidence that PKC pathway activation plays a role in the regulation of RAR-β expression. In these studies a constitutively active PKC-γ augmented the RA-mediated transactivation of a luciferase reporter containing the native RAR-β promoter which has a retinoic-acid-response element (RARE). These findings reveal that PKC pathway activation is an early step in RA-mediated human TC differentiation and that PKC-γ can potentiate the effects of RA on RAR transcriptional activation. © 1993.
Keywords: controlled study; human tissue; cell differentiation; enzyme activation; tumor cells, cultured; transcription regulation; cell membrane; protein kinase c; retinoic acid; cytosol; diglycerides; retinoic acid receptor; tretinoin; teratocarcinoma; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; retinoic acid binding protein; teratocarcinoma differentiation; (human)
Journal Title: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Volume: 1179
Issue: 2
ISSN: 0167-4889
Publisher: Elsevier B.V.  
Date Published: 1993-11-07
Start Page: 203
End Page: 207
Language: English
DOI: 10.1016/0167-4889(93)90142-c
PUBMED: 8218362
PROVIDER: scopus
DOI/URL:
Notes: Source: Scopus
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MSK Authors
  1. Richard N Kolesnick
    236 Kolesnick
  2. Anas Younes
    203 Younes