학술논문

A proliferative melanoma cell phenotype is responsive to RAF/MEK inhibition independent of BRAF mutation status.
Document Type
Article
Source
Pigment Cell & Melanoma Research. Apr2011, Vol. 24 Issue 2, p326-333. 8p. 1 Color Photograph, 2 Diagrams, 1 Chart, 2 Graphs.
Subject
*MELANOMA
*CELL proliferation
*MITOGEN-activated protein kinases
*GENETIC mutation
*CELL culture
Language
ISSN
1755-1471
Abstract
Oncogenic mutations within the MAPK pathway are frequent in melanoma, and targeting of MAPK signaling has yielded spectacular responses in a significant number of patients that last for several months before relapsing. We investigated the effects of two different inhibitors of MAPK signaling in proliferative and invasive melanoma cell cultures with various mutations in the MAPK pathway. Proliferative melanoma cells were more susceptible to pathway inhibition than invasive phenotype cells, irrespective of BRAF mutation status, while invasive phenotype cell response was dependent on BRAF mutation status. Critically, MAPK pathway inhibition of proliferative phenotype cells resulted in acquisition of invasive phenotype characteristics. These results show that melanoma cell phenotype is an important factor in MAPK pathway inhibition response. This suggests that while current therapeutic strategies target proliferative melanoma cells, future approaches should also account for the invasive phenotype population. [ABSTRACT FROM AUTHOR]