INHIBITION OF NUCLEAR FACTOR-KAPPA-B ACTIVITY IS INVOLVED IN E1A-MEDIATED SENSITIZATION OF RADIATION-INDUCED APOPTOSIS

The adenoviral E1A protein has been implicated in the potentiation of apoptosis induced by various external stimuli, but the exact mechanism of that potentiation is not clear. In this study, we compared the sen sitivity to ionizing gamma-irradiation of E1A transfectants with that of parental cells in a human ovarian cancer cell line (SKOV3.ip1); we found that the E1A transfectants became sensitive to radiation-induced apoptosis, Recently, activation of the transcription factor nuclear f actor-kappa B (NF-kappa B) has been shown to play a key role in the an ti-apoptotic pathway of radiation-induced apoptosis. In an attempt to determine whether NF-kappa B was involved in the E1A-mediated sensitiz ation of radiation-induced apoptosis, we found that radiation induced activation of NP-kappa B occurred in the parental cells but was blocke d in the E1A transfectants. Furthermore, parental cells co-transfected with NF-kappa B and E1A were better protected from undergoing apoptos is upon irradiation than those transfected with E1A alone. Thus, our r esults suggest that inhibition of NF-kappa B activation by E1A is a pl ausible mechanism for E1A-mediated sensitization of radiation-induced apoptosis.