Abrogation of TGF-β signaling enhances chemokine production and correlates with prognosis in human breast cancer

Brian Bierie, Christine H. Chung, Joel S. Parker, Daniel G. Stover, Nikki Cheng, Anna Chytil, Mary Aakre, Yu Shyr, Harold L. Moses

研究成果: Article同行評審

101 引文 斯高帕斯(Scopus)

摘要

In human breast cancer, loss of carcinoma cell-specific response to TGF-β signaling has been linked to poor patient prognosis. However, the mechanisms through which TGF-β regulates these processes remain largely unknown. In an effort to address this issue, we have now identified gene expression signatures associated with the TGF-β signaling pathway in human mammary carcinoma cells. The results strongly suggest that TGF-β signaling mediates intrinsic, stromal-epithelial, and host-tumor interactions during breast cancer progression, at least in part, by regulating basal and oncostatin M-induced CXCL1, CXCL5, and CCL20 chemokine expression. To determine the clinical relevance of our results, we queried our TGF-β-associated gene expression signatures in 4 human breast cancer data sets containing a total of 1,319 gene expression profiles and associated clinical outcome data. The signature representing complete abrogation of TGF-β signaling correlated with reduced relapse-free survival in all patients; however, the strongest association was observed in patients with estrogen receptor-positive (ER-positive) tumors, specifically within the luminal A subtype. Together, the results suggest that assessment of TGF-β signaling pathway status may further stratify the prognosis of ER-positive patients and provide novel therapeutic approaches in the management of breast cancer.

原文English
頁(從 - 到)1571-1582
頁數12
期刊Journal of Clinical Investigation
119
發行號6
DOIs
出版狀態Published - 2009 六月 1

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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