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

被引：83

作者：

Khodarev, N. ^{[2
]}

Ahmad, R. ^{[1
]}

Rajabi, H. ^{[1
]}

Pitroda, S. ^{[2
]}

Kufe, T. ^{[1
]}

McClary, C. ^{[1
]}

Joshi, M. D. ^{[1
]}

MacDermed, D. ^{[2
]}

Weichselbaum, R. ^{[2
]}

Kufe, D. ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[2] Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA

来源：

ONCOGENE | 2010年 / 29卷 / 06期

关键词：

MUC1; STAT1; breast cancer; IFN gamma; auto-inductive loop; inflammation; CARCINOMA-ASSOCIATED ANTIGEN; BETA-CATENIN; TRANSCRIPTION FACTOR; C-SRC; APOPTOTIC RESPONSE; GENE-TRANSCRIPTION; DNA-DAMAGE; CELLS; ACTIVATION; EXPRESSION;

D O I：

10.1038/onc.2009.391

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 IFN gamma 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. Oncogene (2010) 29, 920 -929; doi:10.1038/onc.2009.391; published online 16 November 2009

引用

页码：920 / 929

页数：10

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