Il-22-mediated Tumor Growth Reduction Correlates with Inhibition of Erk1/2 and Akt Phosphorylation and Induction of Cell Cycle Arrest in the G2-m Phase.
From: Chirurgische Klinik und Poliklinik der Technischen Universität München, Ismaningerstrasse 22, 81675 Munich, Germany. georgfweber@web.de
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Dec 2006
- ISSN: 0022-1767
- Volume: 177
- Issue: 11
- Pages: 8266-72
- Medium: Print
- Language: English
- Citation (JAMA): Weber Georg F, Gaertner Florian C, Erl Wolfgang, et al. Il-22-mediated Tumor Growth Reduction Correlates with Inhibition of Erk1/2 and Akt Phosphorylation and Induction of Cell Cycle Arrest in the G2-m Phase.. J. Immunol. Dec 2006;177:8266-72
Abstract
IL-22 is a recently discovered cytokine of the IL-10 family that binds to a class II cytokine receptor composed of IL-22R1 and IL-10R2(c) and influences a variety of immune reactions. As IL-22 has also been shown to modulate cell cycle and proliferation mediators such as ERK1/2 and JNK, we studied the role of IL-22 in proliferation, apoptosis, and cell cycle regulation in EMT6 murine breast cancer cells in vitro and in vivo. In this study, we report that murine breast cancer cells express functional IL-22R as indicated by RT-PCR studies, immunoblotting, and STAT3 activation assays. Importantly, IL-22 exposure of EMT6 cells resulted in decreased levels of phosphorylated ERK1/2 and AKT protein kinases, indicating an inhibitory effect of IL-22 on signaling pathways promoting cell proliferation. Furthermore, IL-22 induced a cell cycle arrest of EMT6 cells in the G(2)-M phase. IL-22 reduced EMT6 cell numbers and the proliferation rate by approximately 50% as measured by [(3)H]thymidine incorporation. IL-22 treatment of EMT6 tumor-bearing mice lead to a decreased tumor size and a reduced tumor cell proliferation in vivo, as determined by 3’-deoxy-3’-fluorothymidine-positron emission tomography scans. Interestingly, IL-22 did not induce apoptosis, as determined in annexin V binding assay and caspase-3 activation assay and had no effect on angiogenesis in vivo. In conclusion, our results indicate that IL-22 reduced tumor growth by inhibiting signaling pathways such as ERK1/2 and AKT phosphorylation that promote tumor cell proliferation in EMT6 cells. Therefore, IL-22 may play a role in the control of tumor growth and tumor progression.
Mesh Headings (Keywords): Animals, Apoptosis, Blotting, Western, Breast Neoplasms, Cell Cycle, Cell Line, Tumor, Cell Proliferation, Extracellular Signal-Regulated MAP Kinases, Female, Flow Cytometry, Fluorescent Antibody Technique, Gene Expression, Interleukins, Mice, Oncogene Protein v-akt, Phosphorylation, RNA, Messenger, Receptors, Interleukin, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction
Check for Full Text / PubMed Unique Identifier (PMID): 17114505
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