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- Title
Targeted delivery of NRAS<sup> Q61R</sup> and Cre-recombinase to post-natal melanocytes induces melanoma in Ink4a/Arf<sup> lox/lox</sup> mice.
- Authors
VanBrocklin, Matthew W.; Robinson, James P.; Lastwika, Kristin J.; Khoury, Joseph D.; Holmen, Sheri L.
- Abstract
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.
- Publication
Pigment Cell & Melanoma Research, 2010, Vol 23, Issue 4, p531
- ISSN
1755-1471
- Publication type
Academic Journal
- DOI
10.1111/j.1755-148X.2010.00717.x