Abstract
The retinoblastoma tumor suppressor (RB) restricts cell proliferation by regulating members of the E2F family of transcription factors. In human tumors RB is often inactivated, resulting in aberrant E2F-dependent transcription and uncontrolled proliferation. One of the E2F proteins, E2F1, can also induce apoptosis. The extent of E2F1-induced apoptosis is known to be tissue- and cell-specific, but until now, it has been unclear what variables determine cellular sensitivity to E2F1-induced apoptosis in vivo. A recent study reveals epidermal growth factor receptor (EGFR) signaling to be one such variable, as EGFR signaling cooperates with RB in inhibiting E2F1-induced apoptosis. This finding raises the possibility that therapeutic manipulation of EGFR signaling may specifically trigger the death of cancer cells with inactive RB, thereby enabling "targeted" cancer treatments.
