Gene expression profiles of Herceptin-resistant breast cancer cells

Herceptin (trastuzumab) is a humanized monoclonal antibody targeted to the Her2 receptor tyrosine kinase. Despite a robust response rate to Herceptin-based therapies in Her2-positive patients, resistance frequently arises within one year of the initial response. To address the mechanism of Herceptin resistance, we selected clonal variants of Her2-positive BT474 human breast cancer cells (BT/HerR) that are highly resistant to the anti-proliferative effects of Herceptin in the presence of 0.2 uM or 1.0 uM Herceptin. Our original report on these cell lines demonstrated sustained PI3K/Akt signaling and sensitivity to PI3K inhibitors in BT/HerR cells in the presence of Herceptin, suggesting dysregulation of that pathway as an essential component of Herceptin-resistant proliferation.

10

Gu L, Waliany S, Kane SE