The proliferative and apoptotic activities of E2F1 in the mouse retina

• Published in: Oncogene Vol. 20; no. 48; pp. 7073 - 7084
• Main Authors: LIN, Suh-Chin J, SKAPEK, Stephen X, PAPERMASTER, David S, HANKIN, Mark, LEE, Eva Y.-H. P
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 25.10.2001; Nature Publishing Group
• Subjects: Ageing, cell death; Animals; Apoptosis; Apoptosis - genetics; Apoptosis - physiology; Biological and medical sciences; Cancer; Cell Cycle; Cell Cycle Proteins; Cell Differentiation; Cell Division - genetics; Cell Division - physiology; Cell growth; Cell physiology; Cell proliferation; Cyclin-dependent kinases; Dihydrofolate reductase; DNA Replication; DNA-Binding Proteins; E2F Transcription Factors; E2F-1 protein; E2F1 Transcription Factor; Embryos; Eye Proteins - physiology; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Genes; Genes, Synthetic; Genetic transformation; Humans; Hyperplasia; Interphotoreceptor retinoid-binding protein; Kinases; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular and cellular biology; Mutation; Neurosciences; p53 Protein; Photoreceptor Cells, Vertebrate - metabolism; Photoreceptors; Promoter Regions, Genetic; Proteins; Recombinant Fusion Proteins - physiology; Retina; Retina - embryology; Retina - growth & development; Retina - metabolism; Retina - pathology; Retina - transplantation; Retinal Degeneration - genetics; Retinal Degeneration - pathology; Retinoblastoma; Retinoblastoma protein; Retinoblastoma Protein - deficiency; Retinoblastoma Protein - genetics; Retinoblastoma Protein - physiology; Retinol-Binding Proteins - genetics; Rhodopsin; Rhodopsin - metabolism; Transcription factors; Transcription Factors - physiology; Transcription, Genetic; Transgenes; Transgenic animals; Transgenic mice; Transplants; Tumors; United States > US; Ohio; Cell proliferation; Vertebrata; Mammalia; Mouse; Animal; Rodentia; Retina; Apoptosis
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1204932

The E2F1 transcription factor controls cell proliferation and apoptosis. E2F1 activity is negatively regulated by the retinoblastoma (RB) protein. To study how inactivation of Rb and dysregulated E2F1 affects the developing retina, we analysed wild-type and Rb(-/-) embryonic retinas and retinal transplants and we established transgenic mice expressing human E2F1 in retinal photoreceptor cells under the regulation of the IRBP promoter (TgIRBPE2F1). A marked increase in cell proliferation and apoptosis was observed in the retinas of Rb(-/-) mice and TgIRBPE2F1 transgenic mice. In the transgenic mice, photoreceptor cells formed rosette-like arrangements at postnatal days 9 through 28. Complete loss of photoreceptors followed in the TgIRBPE2F1 mice but not in the Rb(-/-) retinal transplants. Both RB-deficient and E2F1-overexpressing photoreceptor cells expressed rhodopsin, a marker of terminal differentiation. Loss of p53 partially reduced the apoptosis and resulted in transient hyperplasia of multiple cell types in the TgIRBPE2F1 retinas at postnatal day 6. Our findings support the concept that cross-talk occurs between different retinal cell types and that multiple genetic pathways must become dysregulated for the full oncogenic transformation of neuronal retinal cells.