Inactivation of E2f1 enhances tumorigenesis in a Myc transgenic model.
Previous studies have demonstrated both oncogenic and tumor suppressive properties for the E2F1 transcription factor. In this study, E2f1-null mice were crossed with transgenic mice expressing Myc under the control of an epithelial-specific keratin 5 promoter to determine whether the absence of E2F1 would modulate the oncogenic activity of Myc. Inactivation of E2f1 was found to significantly accelerate tumor development in keratin 5 Myc transgenic mice. Acceleration of tumorigenesis occurred despite the fact that apoptosis levels were increased in transgenic tissue and tumors null for E2f1, whereas Myc-induced proliferation was unaffected by the status of E2f1. These findings provide new insight into the tumor suppressive activity of E2F1 and identify for the first time a specific oncogenic alteration that cooperates with the loss of E2F1 in tumorigenesis.
Rounbehler
Robert J
RJ
Department of Carcinogenesis, Science Park-Research Division, University of Texas M. D. Anderson Cancer Center, Smithville, TX 78957, USA.
Rogers
Pamela M
PM
Conti
Claudio J
CJ
Johnson
David G
DG
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000235:genetics; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D016259:Genes, myc / Q000502:physiology; D020022:Genetic Predisposition to Disease; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53