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Breast Cancer Res. 2011 Oct 12;13(5):220. doi: 10.1186/bcr2921.

Signal transducer and activator of transcription 5 as a key signaling pathway in normal mammary gland developmental biology and breast cancer.

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Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Rd NW, Research Building, Room 520A, Washington DC 20057, USA.


STAT5 consists of two proteins, STAT5A/B, that impact mammary cell differentiation, proliferation, and survival. In normal development, STAT5 expression and activity are regulated by prolactin signaling with JAK2/ELF5, EGF signaling networks that include c-Src, and growth hormone, insulin growth factor, estrogen, and progesterone signaling pathways. In cancer, erythropoietin signaling can also regulate STAT5. Activation levels are influenced by AKT, caveolin, PIKE-A, Pak1, c-Myb, Brk, beta-integrin, dystroglycan, other STATs, and STAT pathway molecules JAK1, Shp2, and SOCS. TGF-β and PTPN9 can downregulate prolactin- and EGF-mediated STAT5 activation, respectively. IGF, AKT, RANKL, cyclin D1, BCL6, and HSP90A lie downstream of STAT5.

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