Enhanced G2-M arrest by nuclear factor-κB-Dependent p21waf1/cip1 induction

The transcription factor nuclear factor-kappa B (NF-kappa B) regulates cell survival pathways, but the molecular mechanisms involved are not completely understood. Here, we developed a NF-kappa B reporter cell system derived from CEM T leukemic cells to monitor the consequences of NF-kappa B activation following DNA damage insults. Cells that activated NF-kappa B in response to ionizing radiation or etoposide arrested in the G(2)-M phase for a prolonged time, which was followed by increased cell cycle reentry and survival. In contrast, those that failed to activate NF-kappa B underwent transient G(2)-M arrest and extensive cell death. Importantly, p21(waf1/cip1) was induced in S-G(2)-M phases in a NF-kappa B-dependent manner, and RNA interference of this cell cycle regulator reduced the observed NF-kappa B-dependent phenotypes. Thus, cell cycle-coupled induction of p21(waf1/cip1) by NF-kappa B represents a resistance mechanism in certain cancer cells.