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  • Original Paper
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Stat5 promotes homotypic adhesion and inhibits invasive characteristics of human breast cancer cells

Oncogene volume 24, pages 746–760 (2005)Cite this article

Abstract

Signal transducer and activator of transcription-5 (Stat5) mediates prolactin (PRL)-induced differentiation and growth of breast epithelial cells. We have recently identified active Stat5 as a tumor marker of favorable prognosis in human breast cancer, and determined that Stat5 activation is lost during metastatic progression. Here we provide novel evidence for an invasion-suppressive role of Stat5 in human breast cancer. Activation of Stat5 by PRL in human breast cancer lines was associated with increased surface levels of the invasion-suppressive adhesion molecule E-cadherin in vitro and in xenotransplant tumors in vivo. Inducible E-cadherin was blocked by dominant-negative (Dn) Stat5 or Dn-Jak2, but not by Dn-Stat3. Further experimental data indicated a role of Stat5 as a coordinate regulator of additional invasion-related characteristics of human breast cancer cells, including cell surface association of β-catenin, homotypic cell clustering, invasion through Matrigel, cell migration, and matrix metalloproteinase activity. A role of Stat5 as a suppressor of breast cancer invasion and metastatic progression provides a biological mechanism to explain the favorable prognosis associated with active Stat5 in human breast cancer.

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Acknowledgements

This work was supported by Public Health Service Grants DK52013 and CA101841 (to HR) from the National Institutes of Health (NIH), and DAMD17-03-1-0616 (to ASS) from the US Department of Defense. We thank The Lombardi Comprehensive Cancer Center's shared resources of Microscopy and Imaging, Tissue Culture, and Histology (supported in part by NIH 1P30-CA-51008). We also thank Eva C Andersson for assistance with immunohistochemical analysis of E-cadherin in BT-20 cells.

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  1. Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, NRB E504, 3970 Reservoir Rd NW, Washington, DC, 20057-1469, USA

    Ahmed S Sultan, Jianwu Xie, Matthew J LeBaron, Erica L Ealley, Marja T Nevalainen & Hallgeir Rui

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  1. Ahmed S Sultan
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Correspondence to Hallgeir Rui.

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Sultan, A., Xie, J., LeBaron, M. et al. Stat5 promotes homotypic adhesion and inhibits invasive characteristics of human breast cancer cells. Oncogene 24, 746–760 (2005). https://doi.org/10.1038/sj.onc.1208203

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