Alteration of mRNA expression in breast cancer cells upon chemical inhibition of the 26S proteasome

The 26S proteasome regulates degradation of many cellular proteins to maintain cellular homeostasis. Disruption of proteasome activity followed by dysregulation of tumor suppressors and oncogenes is rampant in many cancers, hence chemical inhibitors of the proteasome have utility as cancer therapeutics, although the underlying mechanisms of their effects in the clinic is poorly understood. We have employed whole genome microarray expression profiling as a discovery platform to identify genes and potential signaling pathways that are affected MCF7 breast cancer cells are treated with MG132 a chemical inhibitor of the proteasome. Total RNA was collected from MCF7 breast cancer cells treated with DMSO (vehicle control) and 1 uM MG132 for 4 or 24H . We identified time dependent changes in the expression of genes enriched in p53 and estrogen receptor pathways, two signatures relevant to breast cancer biology. Proteasome inhibitor induced gene expression in MCF7 breast cancer cells was measured in cells treated with DMSO (vehicle, control) or 1 uM MG132 for 4 and 24 hours. Three independent experiments were performed at each time.