Letter | Published:

Loss of E2F-1 reduces tumorigenesis and extends the lifespan of Rb1(+/−) mice

Nature Geneticsvolume 18pages360364 (1998) | Download Citation



Mutation of the retinoblastoma tumour-suppressor gene (RB) leads to the deregulation of many proteins and transcription factors that interact with the retinoblastoma gene product (pRB), including members of the E2F transcription factor family1,2. As pRB is known to repress E2F transcriptional activity and overexpression of E2F is sufficient for cell cycle progression, it is thought that pRB suppresses growth in part by repressing E2F-mediated transcription3. Previously, we reported that loss of E2f1 in mice results in tissue-specific tumour induction and tissue atrophy4, demonstrating that E2F-1 normally controls growth both positively and negatively in a tissue-specific fashion4,5. To determine whether E2F-1 deregulation—as a result of loss of pRB—promotes proliferation in vivo, we have tested whether loss of E2f1 interferes with the pituitary and thyroid tumorigenesis that occurs in Rb1(+/−) mice6–9. We have found that loss of E2f1 reduces the frequency of pituitary and thyroid tumours, and greatly lengthens the lifespan of Rb1(+/−); E2f1(−/−) animals, demonstrating that E2F-1 is an important downstream target of pRB during tumorigenesis. Furthermore, loss of E2f1 reduces a previously reported strain-dependent difference in Rb1(+/−) lifespan9,10, suggesting that E2f1 or an E2F-1-regulated gene acts as a genetic modifier between the 129/Sv and C57BL/6 strains.

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Author notes

    • Lili Yamasaki

    Present address: Department of Biological Sciences, Columbia University, 1102 Fairchild Bldg, 1212 Amsterdam Avenue, New York, New York, 10027, USA


  1. Massachusetts General Hospital Cancer Center, Bldg 149, 13th Street, Charlestown, Massachusetts, 02129, USA

    • Lili Yamasaki
    • , Nicholas J. Dyson
    •  & Ed Harlow
  2. USDA Human Nutrition Research Center on Aging, Department of Pathology, School of Veterinary Medicine, Tufts University, Boston, Massachusetts, 02111, USA

    • Roderick Bronson
  3. Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Center for Cancer Research, Cambridge, Massachusetts, 02139, USA

    • Bart O. Williams
    •  & Tyler Jacks


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Correspondence to Lili Yamasaki.

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