Inhibition of nuclear factor-kappaB 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 sensitivity 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 factor-kappaB (NF-kappaB) has been shown to play a key role in the anti-apoptotic pathway of radiation-induced apoptosis. In an attempt to determine whether NF-kappaB was involved in the E1A-mediated sensitization of radiation-induced apoptosis, we found that radiation-induced activation of NF-kappaB occurred in the parental cells but was blocked in the E1A transfectants. Furthermore, parental cells cotransfected with NF-kappaB and E1A were better protected from undergoing apoptosis upon irradiation than those transfected with E1A alone. Thus, our results suggest that inhibition of NF-kappaB activation by E1A is a plausible mechanism for E1A-mediated sensitization of radiation-induced apoptosis.
Shao
R
R
Department of Tumor Biology, Breast Cancer Research Program, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Karunagaran
D
D
Zhou
B P
BP
Li
K
K
Lo
S S
SS
Deng
J
J
Chiao
P
P
Hung
M C
MC
D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000528:radiation effects*; D002460:Cell Line; D053938:DNA Fragmentation; D005434:Flow Cytometry; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D014162:Transfection; D014407:Tumor Cells, Cultured
D017500:Adenovirus E1A Proteins; D016328:NF-kappa B