Carcinogen treatment in mouse selectively expressing activated N-Ras(Q61K) in melanocytes recapitulates metastatic cutaneous melanoma development

The incidence of melanoma has significantly increased and a better understanding 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.


Published in:
Pigment cell & melanoma research, 25, 275-278
Year:
2012
ISSN:
1755-148X
Keywords:
Laboratories:




 Record created 2011-12-19, last modified 2018-01-28


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