PMID- 16498399
OWN - NLM
STAT- MEDLINE
DCOM- 20060522
LR  - 20120621
IS  - 0022-202X (Print)
IS  - 0022-202X (Linking)
VI  - 126
IP  - 5
DP  - 2006 May
TI  - Absence of classical MAP kinase pathway signalling in Merkel cell carcinoma.
PG  - 1135-42
AB  - 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.
FAU - Houben, Roland
AU  - Houben R
AD  - Klinik und Poliklinik fur Haut- und Geschlechtskrankheiten, 
      Julius-Maximilians-University Wurzburg, Josef-Schneider-Strasse 2, 97080 
      Wurzburg, Germany. houben_r@klinik.uni-wuerzburg.de
FAU - Michel, Barbara
AU  - Michel B
FAU - Vetter-Kauczok, Claudia S
AU  - Vetter-Kauczok CS
FAU - Pfohler, Claudia
AU  - Pfohler C
FAU - Laetsch, Barbara
AU  - Laetsch B
FAU - Wolter, Manfred D
AU  - Wolter MD
FAU - Leonard, J Helen
AU  - Leonard JH
FAU - Trefzer, Uwe
AU  - Trefzer U
FAU - Ugurel, Selma
AU  - Ugurel S
FAU - Schrama, David
AU  - Schrama D
FAU - Becker, Juergen C
AU  - Becker JC
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (Androgen-Binding Protein)
RN  - 0 (PEBP1 protein, human)
RN  - 0 (Phosphatidylethanolamine Binding Protein)
RN  - EC 2.7.11.1 (BRAF protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Androgen-Binding Protein/analysis
MH  - Carcinoma, Merkel Cell/*metabolism/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - MAP Kinase Signaling System/*physiology
MH  - Mutation
MH  - Phosphatidylethanolamine Binding Protein
MH  - Phosphorylation
MH  - Polymerase Chain Reaction
MH  - Proto-Oncogene Proteins B-raf/genetics
MH  - Skin Neoplasms/*metabolism/pathology
EDAT- 2006/02/25 09:00
MHDA- 2006/05/23 09:00
CRDT- 2006/02/25 09:00
PHST- 2006/02/25 09:00 [pubmed]
PHST- 2006/05/23 09:00 [medline]
PHST- 2006/02/25 09:00 [entrez]
AID - S0022-202X(15)32910-9 [pii]
AID - 10.1038/sj.jid.5700170 [doi]
PST - ppublish
SO  - J Invest Dermatol. 2006 May;126(5):1135-42. doi: 10.1038/sj.jid.5700170.