Figure 1.

Influence of cellular context on the outcome of E2F depletion. Tumor cells commonly exhibit disruption of the pRB pathway, which deregulates E2F function. Loss of E2F activity in tumor cells by treatment with inhibitor molecules (INHIB) prevents tumor growth. In contrast, loss of E2f activity by targeted inactivation (E2f1^−/−/E2f2^−/− DKO) within a non-tumoral cell elicits a DNA damage response (DDR) and genomic instability. Consequently, this abnormal condition leads to apoptosis or senescence in a p53-functional context, but is oncogenic in a p53-deficient context (E2f1^−/−/E2f2^−/−/p53^−/− TKO).