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Breast Cancer Research
Published in: Breast Cancer Research 3/2007

Open Access 01-06-2007 | Research article

Stat3 is tyrosine-phosphorylated through the interleukin-6/glycoprotein 130/Janus kinase pathway in breast cancer

Authors: Marjan Berishaj, Sizhi Paul Gao, Simi Ahmed, Kenneth Leslie, Hikmat Al-Ahmadie, William L Gerald, William Bornmann, Jacqueline F Bromberg

Published in: Breast Cancer Research | Issue 3/2007

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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.
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Metadata
Title
Stat3 is tyrosine-phosphorylated through the interleukin-6/glycoprotein 130/Janus kinase pathway in breast cancer
Authors
Marjan Berishaj
Sizhi Paul Gao
Simi Ahmed
Kenneth Leslie
Hikmat Al-Ahmadie
William L Gerald
William Bornmann
Jacqueline F Bromberg
Publication date
01-06-2007
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 3/2007
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr1680

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