Targeted delivery of NRASQ61R and Cre-recombinase to post-natal melanocytes induces melanoma in Ink4a/Arflox/lox mice.
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.
VanBrocklin
Matthew W
MW
Nevada Cancer Institute, One Breakthrough Way, Las Vegas, NV, USA.
Robinson
James P
JP
Lastwika
Kristin J
KJ
Khoury
Joseph D
JD
Holmen
Sheri L
SL
D000818:Animals; D001287:Attachment Sites, Microbiological; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D019426:Integrases / Q000235:genetics / Q000378:metabolism*; D008544:Melanocytes / Q000378:metabolism*; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism*
D019941:Cyclin-Dependent Kinase Inhibitor p16; C045073:Cre recombinase; D019426:Integrases; D016283:Proto-Oncogene Proteins p21(ras)
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