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Updated: Aug 6, 2026
The Use of Reverse Phase Protein Arrays (RPPA) to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
Functional annotation of IFN-alpha-stimulated gene expression profiles from sensitive and resistant renal cell
Michelle Holko1, Bryan R G Williams
1Department of Cancer Biology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Abstract:
The antiproliferative, antiviral, and immunomodulatory properties of interferons (IFNs) have led to its therapeutic implementation. IFNs effects are mediated by a complex network of signal transducers, culminating in IFN-stimulated gene (ISG) induction. This complexity leads to diverse clinical responses to IFN, from no response to complete regression of disease. Elucidation of ISG induction patterns is, therefore, essential to understand and maximize its therapeutic potential. To correlate ISG expression profiles with IFN responsiveness, two renal cell carcinoma (RCC) cell lines differing in antiviral and apoptotic response to IFN were treated with IFN-alpha for different times, and expression profiles were analyzed using a customized microarray containing 850 unique putative ISGs. Genes with similar kinetics of induction in both cell lines were clustered and analyzed for gene function. Seven sets of coordinately regulated genes were identified by k-means cluster analysis, and significant functional similarities were identified for five of the seven sets. Strikingly, expression of genes associated with transcription temporally preceded expression of those involved in signal transduction. Enhanced antiviral sensitivity to IFN was coincident with sustained expression of ISGs involved in transcriptional regulation. However, no difference in Stat1 activation was observed between the cell lines. Analysis of ISG expression patterns suggests that subtle differences in transcription profiles contribute to differences in IFN responsiveness.
Insights
Interferon (IFN) therapy effectiveness varies. Understanding how interferon-stimulated genes (ISGs) are induced, particularly transcriptional regulators, is key to improving patient responses and therapeutic outcomes.
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- Interferons (IFNs) exhibit antiproliferative, antiviral, and immunomodulatory effects, leading to their therapeutic use.
- IFN efficacy is mediated by complex signaling pathways and the induction of IFN-stimulated genes (ISGs), resulting in varied clinical responses.
Purpose of the Study:
- To correlate Interferon-stimulated gene (ISG) expression profiles with Interferon (IFN) responsiveness in renal cell carcinoma (RCC).
- To elucidate the role of ISG induction patterns in determining diverse clinical outcomes of IFN therapy.
Main Methods:
- Two renal cell carcinoma (RCC) cell lines with differing IFN responses were treated with IFN-alpha.
- Customized microarray analysis of 850 putative ISGs was performed to analyze expression profiles.
- K-means cluster analysis identified seven sets of coordinately regulated genes, with functional analysis performed on five sets.
Main Results:
- Seven clusters of coordinately regulated ISGs were identified, with five exhibiting significant functional similarities.
- Genes involved in transcription were induced before those in signal transduction pathways.
- Sustained expression of ISGs related to transcriptional regulation correlated with enhanced antiviral sensitivity, despite no difference in Stat1 activation.
Conclusions:
- Subtle differences in ISG transcription profiles significantly contribute to variations in IFN responsiveness.
- Understanding ISG induction kinetics is crucial for optimizing IFN therapeutic strategies in diseases like RCC.