Retinoic acid stimulates the protein kinase C pathway before activation of its beta-nuclear receptor during human teratocarcinoma differentiation.
Biochim Biophys Acta
; 1179(2): 203-7, 1993 Nov 07.
Article
em En
| MEDLINE
| ID: mdl-8218362
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-beta 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-gamma) within 5 min. Transient co-transfection studies provided evidence that PKC pathway activation plays a role in the regulation of RAR-beta expression. In these studies a constitutively active PKC-gamma augmented the RA-mediated transactivation of a luciferase reporter containing the native RAR-beta 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-gamma can potentiate the effects of RA on RAR transcriptional activation.
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Base de dados:
MEDLINE
Assunto principal:
Tretinoína
/
Proteína Quinase C
/
Teratocarcinoma
Limite:
Humans
Idioma:
En
Ano de publicação:
1993
Tipo de documento:
Article