Cyclic AMP inhibits TGF beta 1-induced cell-scattering and invasiveness in murine-transformed keratinocytes
Mouse-transformed keratinocytes cultured in the presence of transforming growth factor ?1 (TGF-?1) 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-?1-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. © 2003 Wiley-Liss, Inc.
|Título según WOS:||Cyclic AMP inhibits TGF beta 1-induced cell-scattering and invasiveness in murine-transformed keratinocytes|
|Título según SCOPUS:||Cyclic AMP inhibits TGF?1-induced cell-scattering and invasiveness in murine-transformed keratinocytes|
|Título de la Revista:||INTERNATIONAL JOURNAL OF CANCER|
|Fecha de publicación:||2003|
|Página de inicio:||715|