Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Houben, R; Vetter-Kauczok, CS; Ortmann, S; Rapp, UR; Broecker, EB; Becker, JC.
Phospho-ERK staining is a poor indicator of the mutational status of BRAF and NRAS in human melanoma.
J Invest Dermatol. 2008; 128(8):2003-2012
Doi: 10.1038/jid.2008.30
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- Führende Autor*innen der Med Uni Graz
- Becker Jürgen Christian
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- Abstract:
- Mutated BRAF and NRAS are suspected to contribute to melanomagenesis by activation of extracellular signal-regulated kinase (ERK). To test this notion, we analyzed the presence of phosphorylated ERK1/2 in 170 melanomas with established NRAS/BRAF mutational status and well-documented clinical follow-up by immunohistochemistry. Several notable observations were obtained: (i) phospho-ERK staining was very heterogeneous within the tumor; (ii) in most cases, ERK was phosphorylated in only a minority of tumor cells; (iii) the percentage of phospho-ERK-positive cells was not correlated with the mutational status of NRAS and/or BRAF; (iv) the Raf kinase inhibitor protein (RKIP) was expressed homogeneously in virtually all melanoma samples not reflecting the inhomogeneity of phospho-ERK; and, finally, (v) neither the portion of phospho-ERK-positive tumor cells nor the RKIP staining intensity showed any correlation to the clinical course of the patients. Furthermore, the ability of BRAF mutant melanoma cells to downregulate mitogen-activated protein kinase activation was shown in melanoma cell lines cultured at high densities or under nonadherent conditions. Our findings suggest that mitogen-activated protein kinase (MAPK) activity is subject to regulation even in BRAF/NRAS mutant melanoma cells and that high MAPK pathway signaling may be important only in distinct subsets of tumor cells.
- Find related publications in this database (using NLM MeSH Indexing)
- Cell Line, Tumor -
- Extracellular Signal-Regulated MAP Kinases - metabolism
- Humans -
- Melanoma - genetics Melanoma - metabolism Melanoma - pathology
- Mutation - genetics
- Phosphatidylethanolamine Binding Protein - metabolism
- Proto-Oncogene Proteins B-raf - genetics Proto-Oncogene Proteins B-raf - metabolism
- Proto-Oncogene Proteins p21(ras) - genetics Proto-Oncogene Proteins p21(ras) - metabolism
- Signal Transduction - genetics
- Skin Neoplasms - genetics Skin Neoplasms - metabolism Skin Neoplasms - pathology