V599EB-RAF is an Oncogene in Melanocytes

作者: Claudia Wellbrock , Lesley Ogilvie , Douglas Hedley , Maria Karasarides , Jan Martin

DOI: 10.1158/0008-5472.CAN-03-3433

关键词: Mitogen-activated protein kinaseMAPK/ERK pathwayKinaseSignal transductionOncogeneProto-Oncogene Proteins c-rafProto-Oncogene Proteins B-rafCancer researchBiologyMelanomaOncology

摘要: The oncogenic version of B-RAF, (V599E)B-RAF, is found in approximately 70% human melanomas. However, the role that this oncogene plays melanoma unclear because (V559E)B-RAF also 80% benign nevi. We have examined B-RAF early stages by expressing (V599E)B-RAF cultured melanocytes. In these cells, induced constitutive mitogen activated ERK-activating kinase (MEK) and extracellular signal-regulated (ERK) signaling, 12-O-tetradecanoylphorbol-13-acetate-independent growth, tumorigenicity nude mice. Intriguingly, RAS-transformed melanocytes, depletion did not block MEK-ERK signaling or cell cycle progression. Similarly, blocked cells harboring but RAS. Thus, although can act as a potent through MEK ERK, it required for melanocytes due to innate redundancy within pathway. These findings important implications future therapeutic strategies.

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