1. ¹Klinik und Poliklinik für Haut- und Geschlechtskrankheiten, Julius-Maximilians-University, Würzburg, Germany
2. ²University of Würzburg, Institute for Virology and Immunobiology, Würzburg, Germany

Correspondence: Dr Jürgen C. Becker, Klinik und Poliklinik für Haut- und Geschlechtskrankheiten, Universitätsklinik Würzburg, Josef-Schneider-Street 2, 97080 Würzburg, Germany. E-mail: becker_jc@klinik.uni-wuerzburg.de

³These authors contributed equally to this work

Received 12 September 2006; Revised 1 February 2007; Accepted 6 March 2007; Published online 3 May 2007.

Abstract

Merkel cell carcinoma (MCC) is a rare but highly aggressive tumor of the skin. Recently, we have shown that MCC cells in situ are characterized by a complete absence of mitogen-activated protein kinase (MAPK) pathway signaling, which is preserved in the MCC cell line UISO. Here we present data suggesting that silencing of the MAPK pathway is essential for the survival of MCC cells. Activation of the MAPK pathway could be achieved by inducing a regulatable form of the c-Raf-1 kinase domain in UISO cells. Consequently, MAPK signaling led to morphological changes, loss of actin stress fibers, and induction of apoptosis, which could be prevented by the MAP kinase kinase-specific inhibitor U0126. Hence, despite the fact that activation of the MAPK pathway contributes to oncogenesis in many cancers, it seems to be a negative selection factor for MCC cells. Since ERK phosphorylation was also inducible by the Raf-activating pharmacological agent ZM336372, these results provide new perspectives for potential therapeutics for this highly aggressive tumor.