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Table 2 Tumor-necrosis factor α (TNFα)- and nuclear factor (NF)-κB-related genes associated with the acquisition of docetaxel resistance in MCF-7 breast tumor cells, MDA-MB-231 breast tumor cells, and A2780 ovarian carcinoma cells

From: Alterations in tumor necrosis factor signaling pathways are associated with cytotoxicity and resistance to taxanes: a study in isogenic resistant tumor cells

Gene Direction and magnitude of change in expressiona Role of gene product Refs.
Changes in the expression of TNFα- or NF-κB-related genes in MCF-7TXT10 cells relative to MCF-7CC10 cells
TNF Increased 12.6, 1.43 Binds to TNFR1 to promote cell death and to TNFR2 to stimulate expression of NF-κB-dependent survival genes [54, 55]
TNFSF10 Increased 6.88 TNF-like ligand that binds to DcR2 to activate NF-κB-dependent survival genes; also called TRAIL [56]
TNFRSF19 Increased 16.5, 1.64 Member of the TNF-receptor family that binds to lymphotoxin alpha, activates NF-κB-mediated transcription [57]
TNFRSF14 Increased, 4.24 TNF-receptor family member, interacts with members of the TNFR-associated factor (TRAF) family and activates NF-κB and AP-1 [58]
TNFSF13 Increased, 3.07 Binds to TNFRSF13B to promote NF-κB activation; also called APRIL [59]
BIRC3 Increased, 52.2 Member of a family of proteins that inhibits apoptosis by binding to TNFR-associated factors TRAF1 and TRAF2 [60]
TLR2 Increased, 5.19 Stimulates NF-κB activation [61]
TRIM38 Increased, 4.22, 7.28 Removes Lys63-linked ubiquitin chains from TRAF2 and TRAF6, negatively regulating NF-κB activity [62]
TNFRSF6B Decreased, -2.02 Member of the TNF-receptor superfamily, which, on binding of TNF, inhibits cell proliferation and induces apoptosis [63]
TRAF3IP2 Decreased, -2.14 Associates with and activates I-κB kinase, leading to the liberation of NF-κB from its complex with I-κB [64]
Changes in the expression of TNFα- or NF-κB-related genes in A2780 DXL cells relative to A2780 cells (MTD)
TNFSF13 Increased, 2.10 Binds to TNFRSF13B to promote NF-κB activation; also called APRIL [59]
TNFRSF11B Increased, 2.01 Decoy receptor for the TNF-related apoptosis-inducing ligand TRAIL; confers resistance to TNF- and TRAIL-induced apoptosis [65]
CARD14 Increased, 2.19, 1.31 Associates with guanylate kinase members that interact with BCL10 and activate NF-κB [66]
IRAK4 Increased, 3.70, 3.86 Required for the optimal transduction of IL-1-induced signals, including the activation of IRAK-1, NF-κB, and JNK [67]
TLR1 Increased, 2.79 Acts via MYD88 and TRAF6 to stimulate NF-κB activation, cytokine secretion, and the inflammatory response [68]
TLR6 Increased, 2.26, 1.57 Also acts via MYD88 and TRAF6 to stimulate NF-κB activation, cytokine secretion, and the inflammatory response [68]
BIRC3 Increased, 8.83 Member of a family of proteins that inhibits apoptosis by binding to TNFR-associated factors TRAF1 and TRAF2 [60]
RFFL Increased, 2.15, 2.13 Endosome-associated ubiquitin ligase for RIP and regulates TNF-induced NF-κB activation [69]
TRAF3IP2 Increased, 2.16 Associates with and activates I-κB kinase, leading to the liberation of NF-κB from its complex with I-κB [64]
SMPD3 Decreased, -1.59, -2.03 Translocates to the plasma membrane in response to TNF-α in a time- and dose-dependent manner [70]
SOX9 Decreased, -30.8 Protein whose expression and activity is negatively regulated by TNF-dependent NF-κB activation [71]
Changes in the expression of TNFα- or NF-κB-related genes in docetaxel-resistant MB-231 cells relative to A2780 cells
CAST Increased, 2.44 Inhibits degradation of NF-κB to prolong NF-κB activation [72]
BCL10 Increased, 3.48 Potent activator of NF-κB activity [73]
RPS6KA3 Increased, 5.95 Phosphorylates I-κB and activates NF-κB in response to TNF [74]
MAP2K5 Increased, 3.54 A survival protein highly expressed in MCF-7 breast tumor cells resistant to etoposide and TNF-α [75]
MKNK2 Increased, 1.76 Promotes TNF-α biosynthesis at the posttranscriptional levels [76]
[75]
TNFRSF10B Decreased, -1.67 Also known as TRAIL receptor 2; stimulates apoptosis via FADD [77]
FADD Decreased, -2.00 A component of the caspase 8-activating complex induced by TNF-α binding to TNFR1 [78]
CRADD Decreased, -2.43 An adaptor protein that promotes TNFα-induced apoptosis through interaction with the TNFR1-interacting protein RIP [79]
TRAF1 Decreased, -2.39 Negatively regulates the ability of TNFR2 to promote cell proliferation and NF-κB activation in T cells [80]
MKNK1 Decreased, -2.00 Promotes TNF-α-mediated mRNA degradation [81]
  1. Full-genome oligo-based microarray experiments were performed comparing differences in gene expression between wild-type and docetaxel-resistant MCF-7 cell lines. Differentially expressed genes were then classified into various functional interaction networks, as described in Materials and methods. Information on the identities and roles of genes associated with TNF-α signaling are presented in tabular form, with particular emphasis on the products of genes that are known to play a role in the induction of NF-κB-dependent survival genes or in the inhibition of apoptosis. aNumbers represent the fold increase (positive numbers) or decrease (negative numbers) in expression of the gene as revealed by one or more oligo probes on the Agilent 44K human microarrays.