Abstract:
: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.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Santibáñez JF,Olivares D,Guerrero J,Martínez Jdoi
10.1002/ijc.11457keywords:
subject
Has Abstractpub_date
2003-12-10 00:00:00pages
715-20issue
5eissn
0020-7136issn
1097-0215journal_volume
107pub_type
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journal_title:International journal of cancer
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