Oncogenic Braf induces melanocyte senescence and melanoma in mice.
We show here that inducible expression of Braf(V600E) off the endogenous Braf gene in mouse melanocytes stimulates skin hyperpigmentation and the appearance of nevi harboring senescent melanocytes. Additionally, approximately 70% of Braf(V600E) mice develop melanomas that reproduce many of the cardinal histological and molecular features of human melanoma and whose cells can colonize the lungs of nude mice. We show that the tumor suppressor p16(INK4a) is not required to induce melanocyte senescence and that its loss is not required for tumor progression, although it does regulate tumor penetrance and latency. Thus, we have developed a mouse model of melanoma driven by Braf(V600E) expressed at physiological levels that reflects the genetics and pathology of the human disease.
Dhomen
Nathalie
N
Signal Transduction Team, Cancer Research UK Centre for Cell and Molecular Biology, The Institute of Cancer Research, London, UK.
Reis-Filho
Jorge S
JS
da Rocha Dias
Silvy
S
Hayward
Robert
R
Savage
Kay
K
Delmas
Veronique
V
Larue
Lionel
L
Pritchard
Catrin
C
Marais
Richard
R
D000818:Animals; D002454:Cell Differentiation; D016922:Cellular Senescence; D004195:Disease Models, Animal; D006801:Humans; D007124:Immunoenzyme Techniques; D008544:Melanocytes / Q000166:cytology* / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D009506:Nevus / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf / Q000502:physiology*
C482120:Braf protein, mouse; D048493:Proto-Oncogene Proteins B-raf