HER2-associated radiation resistance of breast cancer stem cells isolated from HER2-negative breast cancer cells

Purpose: To understand the role of HER2-associated signaling network in breast cancer stem cells (BCSCs); using radiation-resistant breast cancer cells and clinical recurrent breast cancers to evaluate HER2-targeted therapy as a tumor eliminating strategy for recurrent HER2 breast cancers. Experimental Design: HER2-expressing BCSCs (HER2/CD44/CD24) were isolated from radiation-treated breast cancer MCF7 cells and in vivo irradiated MCF7 xenograft tumors. Tumor aggressiveness and radiation resistance were analyzed by gap filling, Matrigel invasion, tumorsphere formation, and clonogenic survival assays. The HER2/CD44 feature was analyzed in 40 primary and recurrent breast cancer specimens. Protein expression profiling in HER2/CD44/CD24 versus HER2/CD44/CD24 BCSCs was conducted with 2-D DIGE and HPLC-MS/MS analysis and HER2-mediated signaling network was generated by Research. on September 22, 2017. © 2012 American Association for Cancer clincancerres.aacrjournals.org Downloaded from Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on October 22, 2012; DOI: 10.1158/1078-0432.CCR-12-1436