Nuclear factor-κB, cancer, and apoptosis

NF-κB transcription factor induces drug resistance through MDR1 expression in cancer cells

“…Once activated, NF-kB controls the expression of numerous genes and many of them regulate the apoptotic pathways. Therefore, the resistant phenotype of cancer cells associated with constitutive or induced NF-kB activity has been associated with NF-kBdependent expression of proteins inhibiting the various proapoptotic pathways (Barkett and Gilmore, 1999;Bours et al, 2000). Our present data as well as a recent publication (Kuo et al, 2002) indicate that NF-kB also acts upstream by controlling drug efflux through P-gp expression in cancer cells while previous reports had demonstrated the NF-kB-dependent regulation of P-gp expression in renal tubules or liver which physiologically express the protein (Thevenod et al, 2000;Ros et al, 2001).…”

Upregulation of cyclooxygenase-2 is accompanied by increased expression of nuclear factor-κB and IκB kinase-α in human colorectal cancer epithelial cells

“…This is in agreement with many epidemiological studies, which have demonstrated a 40 -50% decrease in relative risk for colorectal cancer in individuals taking nonsteroidal-antiinflammatory drugs, compared to those not taking these agents. In addition, several lines of experimental evidence indicate that NF-kB may play an important role in the development and/or progression of human cancers: (1) several members of the IkB and NF-kB families derive from genes that are translocated or amplified in human cancers (Bours et al, 2000). These genetic changes can all lead to enhanced NF-kB transcription activity, indicating that NF-kB target genes may be involved in the control of crucial steps for cellular transformation and cancer progression (Bours et al, 2000).…”

“…(2) The v-rel oncogene of the reticuloendotheliosis virus T (Rev-T), the first member of the Rel/NF-kB family to be discovered (Gilmore, 1999;Bours et al, 2000), can directly transform cells in vivo or in vitro. (3) More recently, NF-kB constitutive activity, as observed in Hodgkin's lymphoma cells, has been associated with a mutation in the gene encoding the IkB-inhibitor (Krappmann et al, 1999), which can lead to impaired control of NF-kB activity and hence to enhanced nuclear activity (Bours et al, 2000).…”

“…(3) More recently, NF-kB constitutive activity, as observed in Hodgkin's lymphoma cells, has been associated with a mutation in the gene encoding the IkB-inhibitor (Krappmann et al, 1999), which can lead to impaired control of NF-kB activity and hence to enhanced nuclear activity (Bours et al, 2000). The NF-kB transcription factor is activated in response to a broad range of preapoptotic stimuli (Osborn et al, 1989;Brach et al, 1991;Schreck et al, 1991), dissociates from its attached inhibitory protein IkB and translocates to the nucleus to induce the expression of target genes, including several well-known antiapoptotic genes such as TNF-receptor-associated factor 1 (TRAF1), and TRAF2, cIAPs, manganese superoxide dismutase, A20 and IEX-IL (Wang et al, 1998;Wu et al, 1998).…”

Antiestrogen resistance in breast cancer and the role of estrogen receptor signaling

“…NFkB is the only protein known to induce BRCA2 expression (Welcsh and King, 2001). Several excellent reviews on NFkB signaling are available (Bours et al, 2000;Baldwin, 2001;Karin et al, 2002).…”