E2F1 has both oncogenic and tumor-suppressive properties in a transgenic model

Using a transgenic mouse model expressing the E2F1 gene under the control o f a keratin 5 (K5) promoter, we previously demonstrated that increased E2F1 activity can promote tumorigenesis by cooperating with either a v-Ha-ras t ransgene to induce benign skin papillomas or p53 deficiency to induce spont aneous skin carcinomas. We now report that as K5 E2F1 transgenic mice age, they are predisposed to develop spontaneous tumors in a variety of K5-expre ssing tissues, including the skin, vagina, forestomach, and odontogenic epi thelium. On the other hand, K5 E2F1 transgenic mice are found to be resista nt to skin tumor development following a two-stage carcinogenesis protocol. Additional experiments suggest that this tumor-suppressive effect of E2F1 occurs at the promotion stage and may involve the induction of apoptosis. T hese findings demonstrate that increased E2F1 activity can either promote o r inhibit tumorigenesis, dependent upon the experimental context.