ArticleBMC cancer2012
Stat1 activation attenuates IL-6 induced Stat3 activity but does not alter apoptosis sensitivity in multiple myeloma.
Article in BMC cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Survival Genie 2: a next-generation web server for targeted and single-cell-based survival analyses.Genome medicine · 2026Article
- Exercise-mediated IL-6 downstream effects modulate brain pathology-can exercise training protocols influence the downstream effects?Frontiers in neurology · 2025Review
- A pilot study of 3D tissue-engineered bone marrow culture as a tool to predict patient response to therapy in multiple myeloma.Scientific reports · 2021Observational
- Article
- STAT1 inhibits STAT3 activation in esophageal squamous cell carcinoma.Cancer management and research · 2018Article
- Interleukin 6 protects pancreatic β cells from apoptosis by stimulation of autophagy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Neuroprotective effect of interleukin-6 in a rat model of cerebral ischemia.Experimental and therapeutic medicine · 2015Article
- The clinical and biological significance of STAT1 in esophageal squamous cell carcinoma.BMC cancer · 2014Article
- Article
- Role of the IL-6-JAK1-STAT3-Oct-4 pathway in the conversion of non-stem cancer cells into cancer stem-like cells.Cellular signalling · 2013Article
- Phosphorylation of signal transducer and activator of transcription 1 reduces bortezomib-mediated apoptosis in cancer cells.Cell death & disease · 2013Article
- Elucidating the crosstalk mechanism between IFN-gamma and IL-6 via mathematical modelling.BMC bioinformatics · 2013Article
- The differentiation and plasticity of Tc17 cells are regulated by CTLA-4-mediated effects on STATs.OncoimmunologyArticle
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMultiple myeloma (MM) is at present an incurable malignancy, characterized by apoptosis-resistant tumor cells. Interferon (IFN) treatment sensitizes MM cells to Fas-induced apoptosis and is associated with an increased activation of Signal transducer and activator of transcription (Stat)1. The role of Stat1 in MM has not been elucidated, but Stat1 has in several studies been ascribed a pro-apoptotic role. Conversely, IL-6 induction of Stat3 is known to confer resistance to apoptosis in MM.
methodsTo delineate the role of Stat1 in IFN mediated sensitization to apoptosis, sub-lines of the U-266-1970 MM cell line with a stable expression of the active mutant Stat1C were utilized. The influence of Stat1C constitutive transcriptional activation on endogenous Stat3 expression and activation, and the expression of apoptosis-related genes were analyzed. To determine whether Stat1 alone would be an important determinant in sensitizing MM cells to apoptosis, the U-266-1970-Stat1C cell line and control cells were exposed to high throughput compound screening (HTS).
resultsTo explore the role of Stat1 in IFN mediated apoptosis sensitization of MM, we established sublines of the MM cell line U-266-1970 constitutively expressing the active mutant Stat1C. We found that constitutive nuclear localization and transcriptional activity of Stat1 was associated with an attenuation of IL-6-induced Stat3 activation and up-regulation of mRNA for the pro-apoptotic Bcl-2 protein family genes Harakiri, the short form of Mcl-1 and Noxa. However, Stat1 activation alone was not sufficient to sensitize cells to Fas-induced apoptosis. In a screening of > 3000 compounds including bortezomib, dexamethasone, etoposide, suberoylanilide hydroxamic acid (SAHA), geldanamycin (17-AAG), doxorubicin and thalidomide, we found that the drug response and IC50 in cells constitutively expressing active Stat1 was mainly unaltered.
conclusionWe conclude that Stat1 alters IL-6 induced Stat3 activity and the expression of pro-apoptotic genes. However, this shift alone is not sufficient to alter apoptosis sensitivity in MM cells, suggesting that Stat1 independent pathways are operative in IFN mediated apoptosis sensitization.
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