Development of gene set for IL-6-dependent RB inactivation signature

Our findings suggested that tamxofen resistance induced by RB depletion depends on increased IL-6 production. To elucidate molecular mechanism, we employed whole genome microarray expression profiling as a discovery platform to identify IL-6-dependent RB inactivation signature. RB depleted MCF7 and control MCF7 were cultured with 2 ug/ml anti-IL-6 antibody or IgG, and a 35-gene signature upregulated by RB depletion in an IL-6 dependent manner was identified. This gene set was highly enriched in genes involved in mitochondrial respiration chain. These data revealed that activation of mitochondrial respiration contribute to RB-depletion induced tamoxifen resistance. RB-depletion induced gene expression in MCF-7 cells was measured in the presence of anti-IL-6 antibody or IgG. Three independent experiments were performed.