Stat3 is tyrosine-phosphorylated through the interleukin-6/glycoprotein 130/Janus kinase pathway in breast cancer Journal Article
| Authors: | Berishaj, M.; Gao, S. P.; Ahmed, S.; Leslie, K.; Al-Ahmadie, H.; Gerald, W. L.; Bornmann, W.; Bromberg, J. F. |
| Article Title: | Stat3 is tyrosine-phosphorylated through the interleukin-6/glycoprotein 130/Janus kinase pathway in breast cancer |
| Abstract: | Introduction: Signal transducer and activator of transcription 3 (Stat3) is constitutively tyrosine-phosphorylated in approximately 50% of primary breast carcinomas. A number of different mechanisms responsible for Stat3 activation, including abnormal activation of receptor tyrosine kinases, Src, and Janus kinases (Jaks), have been implicated in breast cancer. Methods: We examined six breast cancer-derived cell lines expressing high or low levels of tyrosine-phosphorylated Stat3 (pStat3) as well as primary breast cancer specimens. Results: Inhibition of Src or EGFR (epidermal growth factor receptor) tyrosine kinases had no effect on pStat3 levels, whereas pan-Jak inhibitor P6 resulted in complete abrogation of Stat3 phosphorylation and inhibition of growth. Jaks are required for cytokine signaling, and the glycoprotein 130 (gp130) receptor-associated Jaks are known mediators of Stat3 phosphorylation. Blockade of the gp130 receptor or sequestration of the interleukin-6 (IL-6) ligand led to a decrease of pStat3 levels. Conditioned media from those cell lines expressing high levels of pStat3 contained IL-6 and were capable of stimulating Stat3 phosphorylation. We examined IL-6 levels in primary breast tumors and found a positive correlation between pStat3 and IL-6 expression. Conclusion: In summary, a principal mechanism of Stat3 activation in breast cancer is through the IL-6/gp130/Jak pathway. © 2007 Berishaj et al.; licensee BioMed Central Ltd. |
| Keywords: | immunohistochemistry; signal transduction; controlled study; protein phosphorylation; unclassified drug; human cell; genetics; protein function; antigen expression; metabolism; stat3 protein; enzyme inhibition; breast cancer; epidermal growth factor receptor; cancer cell culture; enzyme activation; cell line, tumor; protein tyrosine kinase; breast neoplasms; enzyme linked immunosorbent assay; physiology; gene expression regulation; cancer inhibition; gene expression regulation, neoplastic; janus kinase; breast tumor; tumor cell line; interleukin 6; interleukin-6; stat3 transcription factor; enzyme-linked immunosorbent assay; estrogen receptor; progesterone receptor; breast carcinogenesis; glycoproteins; glycoprotein; phosphotyrosine; glycoprotein gp 130; glycoprotein 130, human; janus kinases |
| Journal Title: | Breast Cancer Research |
| Volume: | 9 |
| Issue: | 3 |
| ISSN: | 1465-5411 |
| Publisher: | Biomed Central Ltd |
| Date Published: | 2007-05-01 |
| Start Page: | R32 |
| Language: | English |
| DOI: | 10.1186/bcr1680 |
| PUBMED: | 17531096 |
| PROVIDER: | scopus |
| PMCID: | PMC1929096 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 38" - "Export Date: 17 November 2011" - "CODEN: BCRRC" - "Source: Scopus" |
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