Dermal delivery of constructs encoding Cre recombinase to induce skin tumors in PtenLoxP/LoxP;BrafCA/+ mice
Key findings
Dermal delivery of Cre recombinase-expressing constructs by DNA tattoo administration and particle-mediated gene transfer eliminated spontaneous tumors that occurred in 68% (258/379) of Tyr::CreERT2;PtenLoxP/LoxP;BrafCA/+ mice. DNA tattoo administration of pVAX1/CAG-Cre induced tumors in 100% (12/12) of PtenLoxP/LoxP;BrafCA/+ mice with 27-day mean latency versus 0% (0/6) with promoterless control. Induced melanomas showed equivalent growth kinetics and PLX4720 sensitivity to tamoxifen-induced controls.
Melanocyte-specific tyrosinase promoters prevented keratoacanthomas and squamous cell carcinomas that arose with non-specific CAG promoter delivery. The minimal 577-bp mTyr promoter in pVAX1/mTyr-Cre achieved 75% (6/8) melanoma induction efficiency by DNA tattoo versus 25% (2/8) with 6.1-kb Tyr promoter. Gene gun delivery to ear skin increased mTyr-Cre induction to 100% (4/4), producing highly pigmented Schwann cell-like melanomas with S100+ neural crest markers.