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Cooperativity of the MUC1 oncoprotein and STAT1 pathway in poor prognosis human breast cancer

Oncogene volume 29, pages 920–929 (2010)Cite this article

Abstract

Signal transducer and activator of transcription 1 (STAT1) is activated in the inflammatory response to interferons. The MUC1 oncoprotein is overexpressed in human breast cancers. Analysis of genes differentially expressed in MUC1-transformed cells has identified a network linking MUC1 and STAT1 that is associated with cellular growth and inflammation. The results further show that the MUC1-C subunit associates with STAT1 in cells and the MUC1-C cytoplasmic domain binds directly to the STAT1 DNA-binding domain. The interaction between MUC1-C and STAT1 is inducible by IFNγ in non-malignant epithelial cells and constitutive in breast cancer cells. Moreover, the MUC1–STAT1 interaction contributes to the activation of STAT1 target genes, including MUC1 itself. Analysis of two independent databases showed that MUC1 and STAT1 are coexpressed in about 15% of primary human breast tumors. Coexpression of MUC1 and the STAT1 pathway was found to be significantly associated with decreased recurrence-free and overall survival. These findings indicate that (i) MUC1 and STAT1 function in an auto-inductive loop, and (ii) activation of both MUC1 and the STAT1 pathway in breast tumors confers a poor prognosis for patients.

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Acknowledgements

This work was supported by Grants CA97098 and CA111423 awarded by the National Cancer Institute.

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Author notes

  1. N Khodarev, R Ahmad, R Weichselbaum and D Kufe: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, USA

    N Khodarev, S Pitroda, D MacDermed & R Weichselbaum

  2. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

    R Ahmad, H Rajabi, T Kufe, C McClary, M D Joshi & D Kufe

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  1. N Khodarev
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Correspondence to D Kufe.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Khodarev, N., Ahmad, R., Rajabi, H. et al. Cooperativity of the MUC1 oncoprotein and STAT1 pathway in poor prognosis human breast cancer. Oncogene 29, 920–929 (2010). https://doi.org/10.1038/onc.2009.391

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