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.
authors: Laboratory of Medical Chemistry and Human Genetics, Center for Biomedical Integrated Genoproteomics, University of Liège, Liège, Belgium.
authors: V
authors: V
authors: Benoit
authors: E
authors: E
authors: de Moraes
authors: N A
authors: NA
authors: Dar
authors: E
authors: E
authors: Taranchon
authors: V
authors: V
authors: Bours
authors: A
authors: A
authors: Hautefeuille
authors: P
authors: P
authors: Tanière
authors: A
authors: A
authors: Chariot
authors: J-Y
authors: JY
authors: Scoazec
authors: C V
authors: CV
authors: de Moura Gallo
authors: M-P
authors: MP
authors: Merville
authors: P
authors: P
authors: Hainaut