Activator protein 1 (AP-1)- and nuclear factor kappa B (NF-kappa B)-dependent transcriptional events in carcinogenesis

Citation
Tc. Hsu et al., Activator protein 1 (AP-1)- and nuclear factor kappa B (NF-kappa B)-dependent transcriptional events in carcinogenesis, FREE RAD B, 28(9), 2000, pp. 1338-1348
Citations number
168
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Biochemistry & Biophysics
Journal title
FREE RADICAL BIOLOGY AND MEDICINE
ISSN journal
0891-5849 → ACNP
Volume
28
Issue
9
Year of publication
2000
Pages
1338 - 1348
Database
ISI
SICI code
0891-5849(20000501)28:9<1338:AP1(AN>2.0.ZU;2-D
Abstract
Generation of reactive oxygen species (ROS) during metabolic conversion of molecular oxygen imposes a constant threat to aerobic organisms. Other than the cytotoxic effects, many ROS and oxidants are also potent tumor promote rs linking oxidative stress to carcinogenesis. Clonal variants of mouse epi dermal JB6 cells originally identified for their differential susceptibilit y to tumor promoters also show differential reduction-oxidation (redox) res ponses providing a unique model to study oxidative events in tumor promotio n. AP-1 and NF-kappa B, inducible by tumor promoters or oxidative stimuli, show differential protein levels or activation in response to tumor promote rs in JB6 cells. We further demonstrated that AP-1 and NF-kappa B are both required for maintaining the transformed phenotypes where inhibition of eit her activity suppresses transformation response in JB6 cells as well as hum an keratinocytes and transgenic mouse. NF-kappa B proteins or extracellular signal-regulated kinase (ERK) but not AP-1 proteins are shown to be suffic ient for conversion from transformation-resistant to transformation-suscept ible phenotype. Insofar as oxidative events regulate AP-1 and NF-kappa B tr ansactivation, these oxidative events can be important molecular targets fo r cancer prevention. (C) 2000 Elsevier Science Inc.