Abstract
BackgroundTranscription factors (TFs) are effectors of cell signaling pathways that regulate gene expression. TF networks are highly interconnected; one signal can lead to changes in many TF levels, and one TF level can be changed by many different signals. TF regulation is central to normal cell function, with altered TF function being implicated in many disease conditions. Thus, measuring TF levels in parallel, and over time, is crucial for understanding the impact of stimuli on regulatory networks and on diseases.ResultsHere, we report the parallel analysis of temporal TF level changes due to multiple stimuli in distinct cell types. We have analyzed short-term dynamic changes in the levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), signal transducer and activator of transcription 3 (Stat3), cAMP response element-binding protein (CREB), glucocorticoid receptor (GR), and TATA binding protein (TBP), in breast and liver cancer cells after tumor necrosis factor-alpha (TNF-α) and palmitic acid (PA) exposure. In response to both stimuli, NF-kB and CREB levels were increased, Stat3 decreased, and TBP was constant. GR levels were unchanged in response to TNF-α stimulation and increased in response to PA treatment.ConclusionsOur results show significant overlap in signaling initiated by TNF-α and by PA, with the exception that the events leading to PA-mediated cytotoxicity likely also include induction of GR signaling. These results further illuminate the dynamics of TF responses to cytokine and fatty acid exposure, while concomitantly demonstrating the utility of parallel TF measurement approaches in the analysis of biological phenomena.Electronic supplementary materialThe online version of this article (doi:10.1186/s12896-016-0293-6) contains supplementary material, which is available to authorized users.
Highlights
Transcription factors (TFs) are effectors of cell signaling pathways that regulate gene expression
Having previously demonstrated applicability of our approach to parallel measurement of TFs [23], we sought to apply the technique to furthering our understanding of biological signaling kinetics while demonstrating use of the technique for measuring a broader array of TFs in parallel
TF measurements in MDA-MB-231 breast cancer cells stimulated with Tumor necrosis factor-alpha (TNF-α) We first examined the changes in nuclear TF levels associated with TNF-α stimulation of MDA-MB-231 breast cancer cells
Summary
Transcription factors (TFs) are effectors of cell signaling pathways that regulate gene expression. Measuring TF levels in parallel, and over time, is crucial for understanding the impact of stimuli on regulatory networks and on diseases. Recent advances in cell signaling pathway analysis have led to the advent of a new field of study, systems biology [9]. Systems biology relies on vast amounts of data that can be generated from the various “omics” techniques. These data represent the results of cell signal transduction and would be complemented by parallel measurements of the levels of transcription factors, the upstream mediators of cellular signaling
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