OVEREXPRESSION OF E2F-1 IN RAT EMBRYO FIBROBLASTS LEADS TO NEOPLASTIC TRANSFORMATION

The transcription factor E2F has been implicated in controlling the activation of multiple genes associated with cell proliferation. E2F-1, which is a component of E2F, can promote oncogenesis when transfected into REF cells. The transformation caused by E2F-1 correlates with constitutive overexpression of the transgene, increased transcription of E2F-dependent genes and the enhancement of two E2F DNA binding complexes containing the retinoblastoma susceptibility gene product (Rb) and E2F-1. The oncogenic potential of E2F-1 is dependent on functional DNA binding and transactivation domains but does not require the ability to interact directly with Rb. These findings provide the first direct evidence that sustained unregulated expression of E2F-1 can lead to the loss of cell proliferation control and that E2F-1 is a key component in cell cycle control.