Multiple murine BRaf(V600E) melanoma cell lines with sensitivity to PLX4032.

The BRAF mutation, which approaches 50% in human melanomas, constitutively activates pERK and contributes to disease progression. The BRAF inhibitor, Vemurafenib (PLX4032), shows promising clinical responses, but resistance to PLX4032 usually develops within a year. Transgenic mouse models allow the study of BRaf melanoma , however models are necessary to better understand the molecular mechanism underlying disease progression and resistance. We established melanoma cell lines (D4M cells) from the conditional mouse model of metastatic melanoma: , which recapitulates human disease. Cultured D4M cells express high constitutive pERK. PLX4032 abrogates ERK phosphorylation, inhibits D4M proliferation, and increases expression of the melanoma associated antigen, pmel, , consistent with human BRAF melanoma cell lines. D4M cells are transplantable in either immune-compromised or syngeneic B6 mice. Thus, D4M cell lines allow correlation of studies on molecular mechanisms of melanoma with investigations on pathology and immunology.