Estrogen abrogates zoledronic acid induced gene expression signature in endocrine sensitive tumor cell lines in vitro.

e12570Background: Clinical data from several trials (ABCSG-12, ZO-FAST, AZURE) suggest an improved disease-free survival after the treatment with zoledronic acid (ZO) in adjuvant breast cancer, with an improved overall survival in women after ZO treatment that were more than five years postmenopausal or older than 60 years at baseline. The chief object of the study was to identify the molecular mechanism at genomic, non-genomic and mitochondrial levels that protect hormone-sensitive breast cancer cells from ZO induced cell death. We here report the genomic level. Methods: To identify the most re-sensitive days against estradiol (1nM E2) and Insulin-like growth factor 1 (10ng/ml IGF-1), a proliferation assay was performed using MCF-7, T47D and MDA-MB-231 breast cancer cell lines. EZ4U and SRB assays were used to investigate the influence of several ZO concentrations (0µM, 6.25µM, 12.5µM, 25µM, 50µM and 100µM) and 1nM E2 and 10ng/ml IGF-1 under estrogen-free conditions. Data of a microarray (Affymetrix) wer...