Figure 4

Signaling pathways and proteins that can increase or decrease STAT5 signaling in breast cancer cells. Research to date has identified several factors that can contribute to higher levels of STAT5 activation or, conversely, reduce activation levels in breast cancer cells. As in normal mammary epithelial cells, PRL/JAK2, c-Src, EGF/EGFR, ErbB4, TGF-α, estrogen and progesterone, and IGF pathways can increase STAT5 activation. In breast cancer cells, EPO/EPOR and HOXA1 also have been shown to increase STAT5 signaling. Two cellular proteins shown to increase STAT5 activation in breast cancer cells are breast tumor kinase (Brk) and transcription factor proto-oncogene v-Myb myeloblastosis viral oncogene homolog (avian) (c-Myb). As in normal mammary epithelial cells, caveolin-1 and SOCS-3 can downregulate STAT5 activation; however, in breast cancer cells, PTPN9 (protein tyrosine phosphatase, non-receptor type 9) also has been shown to downregulate STAT5 signaling. c-Src, human cellular-Src; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; EPO, erythropoietin; EPOR, erythropoietin receptor; ErbB4, v-erb-b2 erythroblastic leukemia viral oncogene homolog 4, neuro/glioblastoma-derived oncogene homolog (avian); HOXA1, homeobox A1; IGF, insulin growth factor; JAK2, Janus kinase 2; PRL, prolactin; SOCS-3, suppressor of cytokine signaling 3; STAT5, signal transducer and activator of transcription 5; TGF-α, transforming growth factor-alpha.