E2F1 has both oncogenic and tumor-suppressive properties in a transgenic model.
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.
Pierce
A M
AM
Department of Carcinogenesis, Science Park-Research Division, The University of Texas M. D. Anderson Cancer Center, Smithville, Texas 78957, USA.
Schneider-Broussard
R
R
Gimenez-Conti
I B
IB
Russell
J L
JL
Conti
C J
CJ
Johnson
D G
DG
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D051379:Mice; D018632:Mice, Inbred SENCAR; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D009857:Oncogenes; D056465:Retinoblastoma-Binding Protein 1; D012867:Skin / Q000166:cytology / Q000187:drug effects; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C493754:E2f1 protein, mouse; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D013755:Tetradecanoylphorbol Acetate