ERBB2 and breast carcinoma: For ErbB4 signaling (in Reactome), recently it has been reported that in ErbB2-positive breast cancer cell-lines, ErbB4 was up-regulated at the protein level in vitro and re-activated PI3K-Akt signaling in resistant conditions compared to the sensitive condition, and the knock-down of ErbB4 induced apoptosis in both the lapatinib-resistant and trastuzumab-resistant cell-lines [43].