Skip to main content
Figure 2 | Breast Cancer Research

Figure 2

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

Figure 2

STAT5 can be activated by diverse and sometimes interacting signaling pathways in mammary epithelial cells. Prolactin (PRL) signaling networks dominate in STAT5 activation in normal mammary gland development with contributions from growth hormone (GH), insulin growth factor (IGF), estrogen, epidermal growth factor (EGF), and ErbB4 signaling. PRL and GH work predominantly through their respective receptors prolactin receptor (PR) and growth hormone receptor (GHR) through Janus kinase 2 (JAK2) and are key mediators of pregnancy-induced mammary gland development. Estrogen and EGF acting through respective receptors estrogen receptor-alpha (ERα) and EGF receptor (EGFR) initiate pubertal mammary gland development and contribute to pregnancy-induced development. They can interact through human cellular-Src (c-Src) pathways. Transforming growth factor-alpha (TGF-α) is the second ligand from the EGF family to be shown to influence STAT5 activation levels in normal and cancer cells. IGF signaling through insulin growth factor-related receptors (IGFRs) may also include c-Src and, under some circumstances, JAK2 in both puberty- and pregnancy-induced development. The contribution of ErbB4 to STAT5 signaling is most prominent during lactation. In breast cancer, EGF and estrogen pathways acting through c-Src can drive proliferation and survival. JAK1 has been shown to increase PR/JAK2 activation in some settings. When the erythropoietin receptor (EPOR) is expressed in breast cancer cells and erythropoietin (EPO) is present, they can signal through JAK2 to STAT5 to promote resistance to trastuzumab therapy. ErbB4, v-erb-b2 erythroblastic leukemia viral oncogene homolog 4, neuro/glioblastoma-derived oncogene homolog (avian); STAT5, signal transducer and activator of transcription 5.

Back to article page