Fig. 3.

Key RET signaling and transcriptional interactions in breast cancer. Estrogen regulated gene expression is a key aspect of RET signaling function in ER-positive breast cancer. Additionally, GDNF-RET signaling has been shown to induce estrogen receptor phosphorylation and transcriptional activity. In HER2-positive breast cancer, c-Src mediates a GDNF-dependent interaction between RET and HER2, generating multiple pro-cancer phenotypes in PDX models. In addition to the well-described estrogen regulation of RET expression, inflammatory cytokine signaling has been suggested as an alternate mechanism underlying RET overexpression