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Fig. 3 | Molecular Cancer

Fig. 3

From: Targeting metabolic flexibility via angiopoietin-like 4 protein sensitizes metastatic cancer cells to chemotherapy drugs

Fig. 3

Coordinated transcriptional regulation of multiple ABC transporter genes. a Ingenuity Pathway Analysis (IPA) identified c-Myc and NF-κB as potential transcriptional factors that regulate the expression of multiple ABC transporters when stimulated with recombinant cANGPTL4 protein. IPA-assisted pathways were mapped following experimental kinase inhibitor screen. To avoid bias, all kinases that prevented the up-regulation of ABC transporter expression under the stimulation of cANGPTL4 were analyzed using the Ingenuity Pathway Analysis software. b Representative immunoblot of total and phosphorylated ERK1/2, PKB (Akt), c-Myc and NF-κB from MKN74 cells treated with recombinant cANGPTL4. β-tubulin serves as loading and transfer controls. Loading controls for the immunoblot analyses were from the same sample. c Representative quantitative ChIP assays performed using preimmune IgG (p.i.) or antibodies against phosphorylated NF-κB/p65 and c-Myc in rh-cANGPTL4-treated MKN74 cells. Schematic illustrations show the relative positions of putative NF-κB and Myc binding sites on the regulatory regions of indicated human ABC transporter genes. Putative specific binding sites for respective transcription factors were determined in silico with the Jaspar database. A control region 2 kb upstream of the promoter served as a negative control. Values are represented as mean ± s.d. from n = 3 independent experiments. *P < 0.05, ** P < 0.01. n.s., not significant. d FACS analysis of cell surface expression of ABCB1 (left panel), ABCC1 (middle panel) and ABCG2 (right panel) in recombinant cANGPTL4 (rh-cANGPTL4)-treated MKN74 cells whose c-Myc was suppressed by siRNA (siMYC) and/or NF-κB activity was inhibited by IKK2 inhibitor (IKK2 Inh; 1 μM). Data are represented as mean ± s.d. from 3 independent experiments

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