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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Gefitinib inhibits the growth and invasion of urothelial carcinoma cell lines in which Akt and MARK activation is dependent on constitutive epidermal growth factor receptor activation
Clinical Cancer Research, Volume 12, No. 9, Year 2006
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Description
Purpose: Abnormally high levels of epidermal growth factor receptor (EGFR) protein are associated with advanced tumor stage/grade. The objective of this study was to evaluate the effects of the specific EGFR tyrosine kinase inhibitor gefitinib on activation of the Akt and mitogen-activated protein kinase (MAPK) pathways in human urothelial cell carcinoma (UCC) cell lines and to identify potential markers of gefitinib responsiveness in biopsy samples of UCC. Experimental Design: Changes in markers of UCC growth and invasion after exposure to gefitinib were studied in six human UCC cell lines expressing various levels of EGFR. The findings were related to activation of Akt and MAPK. We studied the influence of gefitinib on intraepithelial expansion of the responsive 1207 cell line. EGFR, Akt, and MAPK activation was studied by Western blot analysis of a panel of 57 human UCC. Results: Gefitinib had a growth-inhibitory and anti-invasive effect in two of six UCC cell lines (i.e., 647V and 1207). Gefitinib was also able to block the expansion of 1207 at the expense of normal urothelial cells. These effects did not depend on the level of expression of EGFR but they were associated with the down-regulation of MAPK and Akt activity; in 1207 cells, gefitinib activity was associated with p27 up-regulation and p21 and matrix metalloproteinase-9 downregulation. Similarly, the Akt and MAPK pathways were found to be strongly phosphorylated in association with EGFR activation in a subset of human UCC specimens. Conclusions: Activation of EGFR, Akt, and MAPK defines a subset of UCC which might provide information for the identification of gefitinib responders. © 2006 American Association for Cancer Research.
Authors & Co-Authors
Nicolle, Gaëlle
France, Creteil
Université Paris-est Créteil Val de Marne
Daher, Ahmad
Lebanon, Beirut
Université Libanaise
Maillé, Pascale
France, Creteil
Université Paris-est Créteil Val de Marne
Vermey, Marcel
Netherlands, Rotterdam
Erasmus Universiteit Rotterdam
Loric, Sylvain
France, Creteil
Université Paris-est Créteil Val de Marne
Bakkar, Ashraf A.
France, Creteil
Université Paris-est Créteil Val de Marne
Wallerand, Hervé
France, Besancon
Centre Hospitalier Universitaire de Besançon
Vordos, Dimitri
France, Creteil
Hôpital Henri Mondor
Vacherot, Francis
France, Creteil
Université Paris-est Créteil Val de Marne
De Medina, Sixtina Gil Diez
France, Creteil
Université Paris-est Créteil Val de Marne
Abboü, Clément Claude
France, Creteil
Hôpital Henri Mondor
van der Kwast, Theodorus H.
Canada, Toronto
Mount Sinai Hospital of University of Toronto
Thiery, Jean Paul
France, Paris
Cnrs Centre National de la Recherche Scientifique
Radvanyi, F.
France, Paris
Cnrs Centre National de la Recherche Scientifique
Chopin, Dominique K.
France, Creteil
Université Paris-est Créteil Val de Marne
France, Creteil
Hôpital Henri Mondor
Statistics
Citations: 15
Authors: 15
Affiliations: 7
Identifiers
Doi:
10.1158/1078-0432.CCR-05-2148
ISSN:
10780432
Research Areas
Cancer