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

Sprowl, Jason A; Reed, Kerry; Armstrong, Stephen R; Lanner, Carita; Guo, Baoqing; Kalatskaya, Irina; Stein, Lincoln; Hembruff, Stacey L; Tam, Adam; Parissenti, Amadeo M

doi:10.1186/bcr3083

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 expression^a	Role of gene product	Refs.
Changes in the expression of TNFα- or NF-κB-related genes in MCF-7_TXT10 cells relative to MCF-7_CC10 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]

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.

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ISSN: 1465-542X

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