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Cell Cycle, Cell Death, and Senescence

The Nuclear Factor-B and p53 Pathways Function Independently in Primary Cells and Transformed Fibroblasts Responding to Genotoxic Damage

The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia

^* To whom correspondence should be addressed. E-mail: gerondakis{at}wehi.edu.au.

	Abstract

With nuclear factor-B (NF-B) and p53 functions generally having disparate outcomes for cell survival and cell division, understanding how these pathways are coordinated following a common activation signal such as DNA damage has important implications for cancer therapy. Conflicting reports concerning NF-B and p53 interplay in different cell line models prompted a reexamination of this issue using mouse primary thymocytes and embryonic fibroblasts, plus fibroblasts transformed by E1A12S. Here, we report that following the treatment of these cells with a range of stress stimuli, p53 and NF-B were found to regulate cell cycling and survival independently. (Mol Cancer Res 2008;6(7):OF1–11)

Key Words: NF-B, p53, apoptosis, radiation, doxorubicin