A mouse model of melanoma driven by oncogenic KRAS.
The small G-protein NRAS is mutated in 22% of human melanomas, whereas the related proteins KRAS and HRAS are mutated in only 2% and 1% of melanomas, respectively. We have developed a mouse model of melanoma in which Cre recombinase/LoxP technology is used to drive inducible expression of (G12V)KRAS in the melanocytic lineage. The mice develop skin hyperpigmentation, nevi, and tumors that bear many of the cardinal histopathology features and molecular characteristics of human melanoma. These tumors invade and destroy the underlying muscles and cells derived from them can grow as subcutaneous tumors and colonize the lungs of nude mice. These data establish that oncogenic KRAS can be a founder event in melanomagenesis.
Milagre
Carla
C
Signal Transduction Team, The Institute of Cancer Research, London, United Kingdom.
Dhomen
Nathalie
N
Geyer
Felipe C
FC
Hayward
Robert
R
Lambros
Maryou
M
Reis-Filho
Jorge S
JS
Marais
Richard
R
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D011905:Genes, ras; D008546:Melanoma, Experimental / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D016283:Proto-Oncogene Proteins p21(ras) / Q000096:biosynthesis / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism
C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)