Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Houben, R; Ortmann, S; Schrama, D; Herold, MJ; Berberich, I; Reichardt, HM; Becker, JC.
Activation of the MAP kinase pathway induces apoptosis in the Merkel cell carcinoma cell line UISO.
J Invest Dermatol. 2007; 127(9):2116-2122
Doi: 10.1038/sj.jid.5700857
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- Führende Autor*innen der Med Uni Graz
- Becker Jürgen Christian
- Co-Autor*innen der Med Uni Graz
- Schrama David
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Actins - metabolism
- Apoptosis -
- Carcinoma, Merkel Cell - enzymology Carcinoma, Merkel Cell - pathology
- Cell Line, Tumor -
- DNA - metabolism
- Enzyme Activation -
- Enzyme Inhibitors - pharmacology
- Gene Expression Regulation, Enzymologic -
- Gene Expression Regulation, Neoplastic -
- Humans -
- MAP Kinase Signaling System -
- Phosphorylation -
- Proto-Oncogene Proteins c-raf - metabolism
- Signal Transduction -
- Skin Neoplasms - enzymology Skin Neoplasms - pathology