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The proliferative and apoptotic activities of E2F1 in the mouse retina

Oncogene volume 20, pages 7073–7084 (2001)Cite this article

Abstract

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.

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Acknowledgements

We thank Dr Jolene Windle for the plasmid pBSKCR3, Nancy Ransom for technical advice and Dr CL Cepko for helpful comment. We appreciate Drs NP Hu's, Y Min's, and E Gerbino's contribution in the early phase of the project. We also wish to thank K Bushnell for proof-reading the manuscript. This work was supported by NIH grants CA49649 to E Lee. Histology was performed in part by a core facility of the San Antonio Cancer Institute (grant #P30 CA 54174).

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Authors and Affiliations

  1. Department of Molecular Medicine/Institute of Biotechnology, University of Texas Health Science Center at San Antonio, TX 78245-3207, Texas, USA

    Suh-Chin J Lin & Eva Y-HP Lee

  2. Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, Tennessee, USA

    Stephen X Skapek

  3. Department of Neuroscience, University of Connecticut Health Science Center, Farmington, CT 06030-3401, Connecticut, USA

    David S Papermaster

  4. Department of Anatomy and Neurobiology, Medical College of Ohio, Toledo, OH 43614, Ohio, USA

    Mark Hankin

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Correspondence to Eva Y-HP Lee.

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Lin, SC., Skapek, S., Papermaster, D. et al. The proliferative and apoptotic activities of E2F1 in the mouse retina. Oncogene 20, 7073–7084 (2001). https://doi.org/10.1038/sj.onc.1204932

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