Gene expression profiling reveals complex changes following MEK-EE expression in cardiac myocytes

The activation of the MEK/ERK pathway has been implicated in the proliferative growth of many tissues, however in the heart it has been linked with hypertrophic growth of the individual cardiac myocytes. We have explored the transcriptional consequences of prolonged ERK1/2 activation in cardiac myocytes following the adenoviral overexpression of a constitutively active form of MEK. MEK-EE. Analysis of microarray data obtained using full rat genome arrays showed > 2000 gene expression changes in response to MEK-EE overexpression for 24 h. We observed similar numbers of genes upregulated and downregulated. The genes were involved in diverse processes including cell structure, metabolism and intracellular signalling. There were also changes in the pro- and ani-apoptotic genes as well as downregulation of the antioxidant enzymes, Mn superoxide dismutase, catalase and thioredoxin 2. Our results reveal the complexity of transcriptional changes that follow the activation of the ERK signalling pathway in these cells and suggest that activation of this MAPK pathway impinges on diverse cellular functions. (c) 2006 Elsevier Ltd. All rights reserved.