Interleukin-1 Receptor Type 2 Acts with c-Fos to Enhance the Expression of Interleukin-6 and Vascular Endothelial Growth Factor A in Colon Cancer Cells and Induce Angiogenesis
| Autor: | Jeng Kai Jiang, Te-Chang Lee, Ai-Chung Mar, Shung Haur Yang, Hui Ju Lee, Jing Jy Cheng, Chun Ho Chu, Chia Wen Chien |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A Angiogenesis Blotting Western Transplantation Heterologous Mice Nude Interleukin 1 receptor type II Biochemistry Cell Line Proinflammatory cytokine Cell Movement Cell Line Tumor Animals Humans Receptors Interleukin-1 Type II Interleukin 6 Molecular Biology Cell Proliferation Tube formation Mice Inbred BALB C Neovascularization Pathologic biology Interleukin-6 Reverse Transcriptase Polymerase Chain Reaction Molecular Bases of Disease Cell migration Cell Biology HCT116 Cells Cell biology Gene Expression Regulation Neoplastic Vascular endothelial growth factor A Colonic Neoplasms biology.protein RNA Interference HT29 Cells Proto-Oncogene Proteins c-fos Intracellular Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 290:22212-22224 |
| ISSN: | 0021-9258 |
| Popis: | Interleukin-1 receptor type 2 (IL1R2) acts as a decoy receptor of exogenous IL-1; however, its intracellular activity is poorly understood. We previously demonstrated that IL1R2 intracellularly activates the expression of several proinflammatory cytokines and affects cell migration. In this study, we found that intracellular IL1R2 expression was increased in human colorectal cancer cells (CRCs) compared with normal colon cells. We also observed that the mRNA levels of IL1R2 were highly correlated with IL-6 in tumor tissues of CRC patients. By modulating its expression in CRC cells, we verified that enhanced IL1R2 expression transcriptionally activated the expression of IL-6 and VEGF-A. Conditioned medium harvested from IL1R2-overexpressing CRC cells contained higher levels of IL-6 and VEGF-A than that from vector control cells and significantly enhanced the proliferation, migration, and tube formation of cultured endothelial cells. We further demonstrated a positive association of intracellular IL1R2 levels with tumor growth and microvessel density in xenograft mouse models. These results revealed that IL1R2 activates the expression of angiogenic factors. Mechanistically, we revealed that IL1R2 complexes with c-Fos and binds to the AP-1 site at the IL-6 and VEGF-A promoters. Together, these results reveal a novel function of intracellular IL1R2 that acts with c-Fos to enhance the transcription of IL-6 and VEGF-A, which promotes angiogenesis in CRC. |
| Databáze: | OpenAIRE |
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