title: Carcinogen treatment in mouse selectively expressing activated N-Ras Q61K in melanocytes recapitulates metastatic cutaneous melanoma development.
abstract: The incidence of melanoma has significantly increased, and a better understanding of its pathogenesis and development of new therapeutic strategies are urgently needed. Here, we describe a murine model of metastatic cutaneous melanoma using C57BL/6 mice expressing a mutated human N-Ras gene under the control of a tyrosinase promoter (TyrRas). These mice were topically exposed to 7,12- dimethylbenzanthracene (DMBA) for brief exposure periods. Cutaneous melanoma developed at the site of exposure on average by 19 weeks of age and in 80% of mice. Importantly, as in humans, melanoma development was associated with subsequent metastasis to tumor-draining lymph nodes. Critically, such metastatic behavior is transplantable, as intradermal inoculation of melanoma cells from TyrRas-DMBA mice into non-transgenic mice led to the growth of melanoma and, again, metastasis to skin-draining lymph nodes. This metastatic melanoma model closely mimics human pathology and should be a useful tool for studying melanoma pathogenesis and developing new therapies.
authors: Dermatology Department, University Hospital, Zürich, Switzerland. emmanuel.contassot@usz.ch
authors: Emmanuel
authors: E
authors: Contassot
authors: Dragana
authors: D
authors: Jankovic
authors: Prisca
authors: P
authors: Schuler
authors: Olivier
authors: O
authors: Preynat-Seauve
authors: Samuel
authors: S
authors: Gehrke
authors: Katrin
authors: K
authors: Kerl
authors: Friedrich
authors: F
authors: Beermann
authors: Lars E
authors: LE
authors: French
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000473:pathology*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics*; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene