MEK5-mediated gene expression changes in PC3 human prostate cancer cells

Mitogen/extracellular signal-regulated kinase kinase-5 (MEK5) belongs to the family of MAP kinases. It is activated by the upstream kinases MEKK2 and MEKK3. MEK5, in turn, phosphorylates and activates extracellular signal-regulated kinase 5 (ERK5) at Thr218/Tyr220. MEK5/ERK5 pathway plays a pivotal role in tumor initiation and progression, including prostate cancer. MEK5 protein is overexpressed in prostate cancer cells compared with normal cells and MEK5 levels are correlated with prostate cancer metastasis. Global gene expression was determined in PC3 cells stably expressing a scrambled (control) shRNA or MEK5 shRNA using the Agilent Mouse Whole Genome microarrays. Gene ontology and pathway analysis of differentially expressed genes using Ingenuity Pathway Analysis and gene set enrichment analysis (GSEA) revealed MEK5 knockdown attenuates a number or critical signaling pathways required for prostate tumor growth and progression. Gene expression was measured in PC3 human prostate cancer cells stably expressing a scrambled shRNA (shControl) or MEK5 shRNA. Three replicates/condition were used.