E2F1 Has Both Oncogenic and Tumor-Suppressive Properties in a Transgenic Model

Abstract

Using a transgenic mouse model expressing the E2F1 gene under the control of a keratin 5 (K5) promoter, we previously demonstrated that increased E2F1 activity can promote tumorigenesis by cooperating with either a v-Ha-ras transgene to induce benign skin papillomas or p53 deficiency to induce spontaneous skin carcinomas. We now report that as K5 E2F1 transgenic mice age, they are predisposed to develop spontaneous tumors in a variety of K5-expressing tissues, including the skin, vagina, forestomach, and odontogenic epithelium. On the other hand, K5 E2F1 transgenic mice are found to be resistant 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. These findings demonstrate that increased E2F1 activity can either promote or inhibit tumorigenesis, dependent upon the experimental context.

ACKNOWLEDGMENTS

We thank Jennifer Smith for technical assistance; Becky Brooks and Shawnda Sanders for preparation of the manuscript; Dale Weiss, Lezlee Coghlan, and coworkers for animal care; and Judy Ing and Chris Yone for artwork.

K5 E2F1 transgenic mice were generated at the NICHD Transgenic Mice Development Facility (NTMDF) at the University of Alabama at Birmingham (contract N01-HD-5-3229). This work was funded by grants from the American Cancer Society (CN-152 to D.G.J.) and the National Institutes of Health (CA 79648 to D.G.J., CA 42157 to C.J.C., NIEHS Center grant ES007784, and CA 16672).