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Nuclear Factor - Kappab-Dependent Regulation of P53 Gene Expression Induced by Daunomycin Genotoxic Drug
Hellin, Anne-Cécile; Calmant, Philippe; Bours, Vincent et al.
1998In Oncogene, 16 (9), p. 1187-95
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Abstract :
[en] Anthracycline drugs are widely used for the treatment of solid tumors and leukemia, but the molecular basis of their biological effect is still poorly understood. In the HCT116 colon carcinoma cell line, which retains a wild-type inducible p53 gene, we show that the anthracycline daunomycin is a potent inducer of p53 and NF-kappaB transcription factors. Nuclear accumulation of p53 protein occurred because of increased protein stability and enhanced gene expression. In addition, daunomycin induced the p53 promoter through the binding of p50/p65 NF-kappaB heterodimers to the kappaB site in the p53 promoter. Under our conditions, the free radical scavengers NAC and PDTC were not able to block NF-kappaB activation or p53 induction, indicating that reactive oxygen intermediates were not involved in the cellular response to daunomycin stimulation. Overexpression of a stable unresponsive IkappaBalpha mutant in HCT116 cells resulted in a complete inhibition of the NF-kappaB activation but only a partial impairment of the p53 protein accumulation induced by daunomycin. We conclude that the p53-activating signal generated by daunomycin is partially regulated by NF-kappaB.
Disciplines :
Oncology
Author, co-author :
Hellin, Anne-Cécile ;  Centre Hospitalier Universitaire de Liège - CHU > Génétique
Calmant, Philippe ;  Centre Hospitalier Universitaire de Liège - CHU > Hématologie biologique et immuno hématologie
Bours, Vincent ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Génétique générale et humaine
Merville, Marie-Paule ;  Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Gielen, Jacques
Language :
English
Title :
Nuclear Factor - Kappab-Dependent Regulation of P53 Gene Expression Induced by Daunomycin Genotoxic Drug
Publication date :
05 March 1998
Journal title :
Oncogene
ISSN :
0950-9232
eISSN :
1476-5594
Publisher :
Nature Publishing Group, United Kingdom
Volume :
16
Issue :
9
Pages :
1187-95
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 27 January 2009

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