Inducible BRAF suppression models for melanoma tumorigenesis.
Somatic mutations in BRAF have been reported in 50 to 70% of melanomas. The most common mutation is a valine to glutamic acid substitution at codon 600 (V600E). (V600E)BRAF constitutively activates ERK signaling and promotes proliferation, survival, and tumor growth. However, although BRAF is mutated in up to 80% of benign nevi, they rarely progress into melanoma. This implicates the BRAF mutation to be an initiating event that requires additional lesions in the genome for full-blown progression to melanoma. Even though the mutations appear early during the pathogenesis of melanoma, targeted BRAF knockdown using inducible shRNA in melanoma cell lines with BRAF mutations shows that BRAF is required for growth and maintenance of tumor in xenograft models.
Hoeflich
Klaus P
KP
Genentech Inc., Department of Molecular Biology, South San Francisco, CA, USA.
Jaiswal
Bijay
B
Davis
David P
DP
Seshagiri
Somasekar
S
D000818:Animals; D045744:Cell Line, Tumor; D005822:Genetic Vectors; D006801:Humans; D008545:Melanoma / Q000209:etiology* / Q000503:physiopathology; D051379:Mice; D009362:Neoplasm Metastasis / Q000503:physiopathology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000502:physiology*
D048493:Proto-Oncogene Proteins B-raf