Cyclic AMP inhibits TGFbeta1-induced cell-scattering and invasiveness in murine-transformed keratinocytes.
Int J Cancer
; 107(5): 715-20, 2003 Dec 10.
Article
em En
| MEDLINE
| ID: mdl-14566820
Mouse-transformed keratinocytes cultured in the presence of transforming growth factor beta1 (TGF-beta1) acquire an array of morphologic and functional properties that give rise to a migratory phenotype that expresses mesenchymal molecular markers. This cellular conversion involves activation of the Ras-ERK pathway, enhancement of urokinase (uPA) and matrix metalloproteinase-9 (MMP-9) expression and induction of invasiveness. In our present work, we demonstrate that cAMP and forskolin are able to prevent the expression of these mesenchymal properties, probably due to blockade of the Ras-ERK pathway. Our results also show that cAMP and forskolin are able to abolish the TGF-beta1-induced reorganization of the actin cytoskeleton that is characteristic of the mesenchymal phenotype and also inhibits the disruption of the E-cadherin cell to cell interactions. The latter responses seem to depend on the activity of protein kinase A, as demonstrated by the activation of the Ras-ERK pathway by specific protein kinase A inhibitors.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Queratinócitos
/
Transformação Celular Neoplásica
/
Fator de Crescimento Transformador beta
/
AMP Cíclico
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Cancer
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Chile
País de publicação:
Estados Unidos