A functionally significant cross-talk between androgen receptor and ErbB2 pathways in estrogen receptor negative breast cancer.

摘要: Abstract Recent studies have identified novel subgroups in ER-negative breast cancer based on the expression pattern of androgen receptor (AR). One subtype (molecular apocrine) has an over-expression steroid-response genes and ErbB2. Using cell lines with molecular apocrine features, we demonstrate a functional cross-talk between AR ErbB2 pathways. We show that stimulation pathways leads to cross-regulation gene for , FOXA1 XBP1 TFF3 KLK3 . As opposed physiologic transient phosphorylation extracellular signal–regulated kinase (ERK1/2) observed testosterone treatment, addition inhibition persistent ERK1/2, which negatively regulates downstream signaling growth. This suggests mechanism involving ERK pathway. Moreover, stimulates proliferation lines, this effect can be reversed using antiandrogen flutamide anti-ErbB2 AG825. Conversely, growth stimulatory heregulin also inhibited flutamide, suggesting affecting proliferation. Importantly, there is synergy combined use AG825 apoptosis, indicates therapeutic advantage blockage