Abstract 4598: Temporal changes of gene expression in breast cancer cells during adaptation to estrogen deprivation highlight the clinical potential for targeting kinase pathways

Aromatase inhibitors (AI) have improved the treatment of estrogen receptor positive (ER+) early and advanced breast cancer (BC). However, the efficacy of AIs is limited by disease progression or relapse. No data is available assessing the temporal changes in gene expression during the development of acquired resistance to long-term estrogen deprivation (LTED). To model the adaptive changes associated with resistance to AI therapy, ER+ human BC cells MCF7 were cultured in the absence of estrogen (E). Genome-wide expression analysis using Illumina 48K arrays was performed to assess changes in gene expression during adaptation at 10 time-points up to 40 weeks (wks). Strikingly, the expression of a proliferation metagene showed resistance to E-deprivation occurred as early as 9 wks. Validation by global assessment of gene expression, revealed a stabilisation of the gene signatures after this time-point. Further analyses were restricted to a triangular pairwise comparison: wt MCF7 cells (modelling pre-treatment), 1 wk post E-deprivation (on AI treatment) and at 9 wks (clinical relapse). Comparison of wt MCF7 versus 1 wk showed 2158 genes were down-regulated and 1724 genes were up-regulated (p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4598.