@article{c8fb0e781b8f461f8b1b73bb41f8b7b6,
title = "Transcriptional activation of cyclooxygenase-2 by tumor suppressor p53 requires nuclear factor-kappaB",
abstract = "Overexpression of cyclooxygenase-2 (Cox-2) is thought to exert antiapoptotic effects in cancer. Here we show that the tumor suppressor p53 upregulated Cox-2 in esophageal and colon cancer cell lines by inducing the binding of nuclear factor-kappaB (NF-kappaB) to its response element in the COX-2 promoter. Inhibition of NF-kappaB prevented p53 induction of Cox-2 expression. Cooperation between p53 and NF-kappaB was required for activation of COX-2 promoter in response to daunomycin, a DNA-damaging agent. Pharmacological inhibition of Cox-2 enhanced apoptosis in response to daunomycin, in particular in cells containing active p53. In esophageal cancer, there was a correlation between Cox-2 expression and wild-type TP53 in Barrett's esophagus (BE) and in adenocarcinoma, but not in squamous cell carcinoma (P<0.01). These results suggest that p53 and NF-kappaB cooperate in upregulating Cox-2 expression, promoting cell survival in inflammatory precursor lesions such as BE.",
keywords = "Barrett's metaplasia, Cyclooxygenase-2, Esophageal cancer, NF-kappaB, p53",
author = "V. Benoit and {De Moraes}, E. and Dar, {N. A.} and E. Taranchon and V. Bours and A. Hautefeuille and P. Tani{\`e}re and A. Chariot and Scoazec, {J. Y.} and {De Moura Gallo}, {C. V.} and Merville, {M. P.} and P. Hainaut",
note = "Funding Information: We thank Mrs G Martel-Planche and Mrs N Lyandrat for technical assistance with TP53 mutation analysis and immunohistochemistry, respectively. We are also grateful to Dr X de Leval (Laboratory of Pharmaceutical Chemistry, University of Li{\`e}ge, Belgium) for providing Cox-2 inhibitors. E de Moraes was supported by a PhD fellowship from CAPES-COFECUB. V Benoit, M-P Merville and A Chariot, are respectively, senior research assistant and research associates at the National Fund for Scientific Research (Belgium). NA Dar is supported by a Special Training Award from IARC. This research was supported by {\textquoteleft}subvention libre{\textquoteright} from ARC (French Association Against Cancer) and by grants from Leon Fredericq Foundation, {\textquoteleft}Centre Anticanc{\'e}reux de l{\textquoteright}Universit{\'e} de Li{\`e}ge, T{\'e}l{\'e}vie, Belgian Federation against cancer and National Fund for Scientific Research (Belgium).",
year = "2006",
month = sep,
day = "21",
doi = "10.1038/sj.onc.1209579",
language = "English",
volume = "25",
pages = "5708--5718",
journal = "Oncogene",
issn = "0950-9232",
number = "42",
}