Differential regulation of P53 and Bcl-2 expression by ultraviolet A and B.
The induction of apoptosis by ultraviolet (UV) radiation and other DNA damaging agents plays a critical role in monitoring the accumulation of genetic damage and the suppression of tumor development. We hypothesize that UVA and UVB induce apoptosis by modulating balances between p53 and/or bcl-2 genes. Using MCF-7 cells that express both wild-type P53 and Bcl-2 proteins, we demonstrated that UVA and UVB induced apoptosis through regulating expression of apoptosis promoting or inhibiting genes. UVA induced immediate apoptosis and downregulated bcl-2 expression. Bcl-2 expression was reduced by approximately 40% at 4 h post-150 kJ UVA irradiation per m2 with a maximum downregulation (over 70%) at 24 h. The dose-response studies revealed that significant reduction of bcl-2 expression was observed at UVA doses ranging from 50 to 200 kJ per m2; however, p53 levels were not affected by UVA. In contrast, UVB exhibited a entirely different action than UVA in that UVB substantially induced p53 expression, but had no effect on bcl-2 expression. The induction of P53 by UVB was dose and time dependent with the maximum expression at 24 h post-2 and post-4 kJ UVB irradiation per m2. Down-regulation of bcl-2 and fragmentation of DNA induced by UVA occurred earlier (approximately at 4 h) than upregulation of p53 and DNA fragmentation by UVB (12-24 h). These results suggest that UVA and UVB cause cell damage through different mechanisms and that the balances between the expression of p53 and bcl-2 may play an important role in regulating the apoptosis induced by UV irradiation.
Wang
Y
Y
Department of Dermatology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Rosenstein
B
B
Goldwyn
S
S
Zhang
X
X
Lebwohl
M
M
Wei
H
H
D017209:Apoptosis / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects; D053938:DNA Fragmentation; D005786:Gene Expression Regulation / Q000528:radiation effects*; D019254:Genes, bcl-2; D016158:Genes, p53; D006801:Humans; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays