Grant: $128,189 - National Institutes of Health - Sep. 25, 2009
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Award Description: Research
Project Description: Signaling through the RAF-MEK-ERK1/2 MAP kinase pathway is critical for a wide variety of biological processes in both normal and disease states. Our long term goal is to determine mechanisms underlying regulation of this pathway and identify the downstream targets of ERK1/2 that contribute to migration, cell proliferation and cell survival. We utilize a primary human melanocyte and melanoma cell model because there are important differences in the signaling through this pathway between normal (melanocytes) and cancerous (melanoma) cells. Mutations in B-RAF are found in 50-70% of melanomas and lead to hyperactivation of the MEK-ERK1/2 pathway and nuclear accumulation of ERK1/2 in an adhesion independent manner. By contrast, activation of ERK1/2 is adhesion-dependent in primary human melanocytes. The goals of this application are to determine the regulation and roles of nuclear ERK1/2 in human melanoma cells. In Specific Aim 1, we will utilize an RNA interference approach to identify importins that regulate the nuclear localization of activated ERK1/2 in human melanoma cells. In Specific Aim 2, we will determine the role of Ets family transcription factors in B-RAF-regulated Rnd3 expression. In Specific Aim 3, we will determine the dependence of mutant B-RAF melanoma cells on B-RAF activity utilizing clinical grade inhibitors in 3-D systems in the absence /presence of stromal cells. We expect to identify new mechanisms underlying regulation of the ERK1/2 and ERK1/2 controlled events which will have important ramifications for signal transduction in normal and disease-states.
Jobs Summary: None created at this time as project is not started. (Total jobs reported: 0)
Project Status: Not Started
This award's data was last updated on Sep. 25, 2009. Help expand these official descriptions using the wiki below.