Breast cancer cells resistant to hormone deprivation maintain an estrogen receptor alpha-dependent, E2F-directed transcriptional program

A significant fraction of breast cancers exhibit de novo or acquired resistance to estrogen deprivation. To model resistance to aromatase inhibitor (AI) therapy, long-term estrogen-deprived (LTED) derivatives of MCF-7 and HCC-1428 cells were generated through culture for 3 and 7 months under hormone-depleted conditions, respectively. These LTED cells showed sensitivity to the ER downregulator fulvestrant under hormone-depleted conditions, suggesting continued dependence upon ER signaling for hormone-independent growth. To evaluate the role of ER in hormone-independent growth, LTED cells were treated +/- 1 uM fulvestrant x 48 h before RNA was harvested for gene expression analysis. MCF-7/LTED and HCC-1428/LTED cells were treated with 10% DCC-FBS with or without the estrogen receptor antagonist drug fulvestrant for 48 hrs prior to RNA harvest for array analysis. Three replicates per condition.