Titre
The tumor promoter 12-O-tetradecanoylphorbol-13-acetate and the ras oncogene modulate expression and phosphorylation of gap junction proteins.
Type
article
Institution
Externe
Périodique
Auteur(s)
Brissette, J.L.
Auteure/Auteur
Kumar, N.M.
Auteure/Auteur
Gilula, N.B.
Auteure/Auteur
Dotto, G.P.
Auteure/Auteur
Liens vers les personnes
ISSN
0270-7306
Statut éditorial
Publié
Date de publication
1991
Volume
11
Numéro
10
Première page
5364
Dernière page/numéro d’article
5371
Langue
anglais
Résumé
Gap junctional intercellular communication is inhibited in response to tumor promoters and oncogene transformation, suggesting that loss of this function is an important step in tumor formation. To elucidate the molecular mechanisms responsible for this inhibition, we examined the expression of gap junction proteins and mRNA in mouse primary keratinocytes after treatment with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and/or ras transformation. During normal cell growth, keratinocytes expression the alpha 1 (connexin 43) and beta 2 (connexin 26) proteins. Within 5 min of TPA treatment, the alpha 1 protein became rapidly phosphorylated on serine residues and its expression was dramatically reduced by 24 h. The beta 2 protein, after an initial increase in expression, was also significantly reduced 24 h after treatment with TPA. ras transformation caused changes similar to those induced by TPA. The alpha 1 protein underwent an increase in serine phosphorylation, although its expression declined only slightly, while beta 2 expression was greatly reduced. The effects of TPA and ras on alpha 1 expression were additive; treatment of ras-transformed cells with TPA resulted in increased alpha 1 phosphorylation, with greatly decreased protein levels, much lower than those generated by either agent alone. These data provide a likely explanation for the similar and synergistic inhibition of gap junctional intercellular communication by phorbol esters and ras.
Sujets
PID Serval
serval:BIB_EEFDDD2096E1
PMID
Date de création
2008-01-24T13:58:49.925Z
Date de création dans IRIS
2025-05-21T06:43:02Z