Skin Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Skin Cancer, including details on identification, causes, prevention, treatment. | ||||||||
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Absence of classical MAP kinase pathway signalling in Merkel cell carcinoma.Houben R, Michel B, Vetter-Kauczok CS, Pföhler C, Laetsch B, Wolter MD, Leonard JH, Trefzer U, Ugurel S, Schrama D, Becker JC Klinik und Poliklinik für Haut- und Geschlechtskrankheiten, Julius-Maximilians-University Würzburg, Josef-Schneider-Strasse 2, 97080 Würzburg, Germany. houben_r@klinik.uni-wuerzburg.de Merkel cell carcinoma (MCC) is a highly metastatic skin tumor. To assess the relevance of the Ras/Raf/MEK/MAP kinase pathway, we analyzed for activating B-Raf mutations and we elucidated the presence of the Raf Kinase Inhibitor Protein (RKIP) and extracellular signal-regulated kinase (ERK) as well as the phosphorylation status of ERK. All MCC samples were negative for the B-Raf(V600E) mutation. Remarkably, RKIP, which was shown to interfere with the activation of MEK by Raf, was highly expressed in primary as well as in metastatic MCC. Immunohistochemical analysis of the phosphorylation status of ERK revealed in 42 out of 44 samples a complete lack of activated ERK in the tumor cells although ERK is expressed; in the two positive cases phosphorylated ERK was restricted to a minor fraction of the tumor cells. Western blot analysis of three MCC-derived cell lines revealed in one case the pattern present in situ (i.e. high RKIP expression and complete absence of phosphorylated ERK). In summary, our data demonstrate the inactivity of the classical MAP kinase signal transduction pathway in MCC, which seems to be because of lack of activation as well as active deactivation. These findings should be accounted for in future therapeutic approaches for this tumor. Published 18 April 2006 in J Invest Dermatol, 126(5): 1135-42.
© 2004-2008 Skin Cancer Research Today. All Rights Reserved. |
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