Cooperativity of the MUC1 oncoprotein and STAT1 pathway in poor prognosis human breast cancer.
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Date
2009Author
Khodarev, N
Ahmad, R
Rajabi, H
Pitroda, S
Kufe, T
McClary, C
Joshi, MD
MacDermed, D
Weichselbaum, R
Kufe, D
Type
ArticleLanguage
enMetadata
Show full item recordAbstract
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 IFNgamma 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.
URI
www.ncbi.nlm.nih.gov/pubmed/19915608http://erepository.uonbi.ac.ke:8080/xmlui/handle/123456789/53022
Citation
Oncogene. 2010 Feb 11;29(6):920-9. doi: 10.1038/onc.2009.391. Epub 2009 Nov 16.Publisher
University of Nairobi Faculty of medicine
Collections
- Faculty of Health Sciences (FHS) [10387]