Reinitiated expression of EJras transgene in targeted epidermal cells of transgenic rabbits by cottontail rabbit papillomavirus infection

Transgenic rabbits carrying the EJras oncogene have been established in our laboratory (Am. J. Pathol. 155 (1999) 315). The expression of the ras gene is targeted to the epidermal keratinocytes using the upstream regulatory r egion (URR) of the cottontail rabbit papillomavirus (CRPV). All of the tran sgenic rabbits develop keratoacanthomas at multiple sites in the skin at 2- 3 days after birth, and the tumors spontaneously regress in 1.5-2 months. W ith regression of the keratoacanthomas, the rabbits appear normal and EJras expression is undetectable in their skin. To determine if CRPV infection w ould reinitiate the expression of the EJras transgene and make the rabbits more sensitive to tumorigenesis, the rabbits were infected with CRPV at 2 m onths of age when the keratoacanthomas had regressed. This study shows that CRPV infection of the transgenic rabbit skin could shorten the latency req uired for CRPV papilloma initiation, and significantly increase the tumor g rowth and persistence rate compared with non-transgenic rabbits. Furthermor e, EJras expression became detectable in the CRPV induced papillomas in tra nsgenic rabbits, but not in the papillomas of non-transgenic rabbits. These results indicate that CRPV infection is able to reinitiate the expression of the CRPV URR controlled EJras oncogene carried by the transgenic rabbits and that the expression of EJras can enhance the tumorigenesis of CRPV inf ection. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.