title: Inducible BRAF suppression models for melanoma tumorigenesis.
abstract: 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.
authors: Genentech Inc., Department of Molecular Biology, South San Francisco, CA, USA.
authors: Klaus P
authors: KP
authors: Hoeflich
authors: Bijay
authors: B
authors: Jaiswal
authors: David P
authors: DP
authors: Davis
authors: Somasekar
authors: S
authors: Seshagiri
mesh_terms: 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*
chemical_list: D048493:Proto-Oncogene Proteins B-raf