Fig. 1

The interaction between ERβ and PI3-K/Akt signaling. Heregulin-β binds to HER2/HER3 receptors, which leading to the PI3-K/Akt signaling activation. The enhancement of PI3-K/Akt signaling triggers the recruitment of the E3 ubiquitin ligase MDM2 to ERβ, which is further stabilized by CBP, resulting in ERβ polyubiquitination. On the contrary, expression of ERβ results in a decrease in Akt signaling by increasing PTEN levels and decreasing protooncogene HER2/HER3 signaling