Phospho-ERK staining is a poor indicator of the mutational status of BRAF and NRAS in human melanoma
| Autor: | Ulf R. Rapp, Sonja Ortmann, Juergen C. Becker, Eva B. Broecker, Claudia S. Vetter-Kauczok, Roland Houben |
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| Rok vydání: | 2008 |
| Předmět: |
Neuroblastoma RAS viral oncogene homolog
MAPK/ERK pathway Proto-Oncogene Proteins B-raf Skin Neoplasms Phosphatidylethanolamine Binding Protein Dermatology Biology Biochemistry Proto-Oncogene Proteins p21(ras) Cell Line Tumor medicine Humans Protein kinase A Extracellular Signal-Regulated MAP Kinases Molecular Biology neoplasms Melanoma Kinase Cell Biology medicine.disease Cell culture Mitogen-activated protein kinase Mutation biology.protein Cancer research Immunohistochemistry Signal Transduction |
| Zdroj: | The Journal of investigative dermatology. 128(8) |
| ISSN: | 1523-1747 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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