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Targeted delivery of NRAS Q61R and Cre ‐recombinase to post‐natal melanocytes induces melanoma in Ink4a/Arf lox/lox mice
Author(s) -
VanBrocklin Matthew W.,
Robinson James P.,
Lastwika Kristin J.,
Khoury Joseph D.,
Holmen Sheri L.
Publication year - 2010
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/j.1755-148x.2010.00717.x
Subject(s) - neuroblastoma ras viral oncogene homolog , cancer research , kras , melanoma , carcinogenesis , cre recombinase , biology , cancer , mutation , gene , transgene , genetics , genetically modified mouse
Summary We have developed a somatic cell gene delivery mouse model of melanoma that allows for the rapid validation of genetic alterations identified in this disease. A major advantage of this system is the ability to model the multi‐step process of carcinogenesis in immune‐competent mice without the generation and cross breeding of multiple strains. We have used this model to evaluate the role of RAS isoforms in melanoma initiation in the context of conditional Ink4a/Arf loss. Mice expressing the tumor virus A (TVA) receptor specifically in melanocytes under control of the dopachrome tautomerase (DCT) promoter were crossed to Ink4a/Arf lox/lox mice and newborn DCT‐TVA/ Ink4a/Arf lox/lox mice were injected with retroviruses containing activated KRAS , NRAS and/or Cre ‐recombinase. No mice injected with viruses containing KRAS and Cre or NRAS alone developed tumors; however, more than one‐third of DCT‐TVA/ Ink4a/Arf lox/lox mice injected with NRAS and Cre viruses developed melanoma and two‐thirds developed melanoma when NRAS and Cre expression was linked.