To elucidate the underlying mechanism, we explored the regulation of IGF-1R signaling using Herceptin-resistant sublines SKBR3-pool2 (pool2) and BT474-HR20 (HR20), derived from SKBR3 and BT474, respectively, two well-known HER2-positive breast cancer cell lines sensitive to Herceptin24. Here, ERBB2 is linked to breast cancer.