Developing a strategy to define the effects of insulin-like growth factor-1 on gene expression profile in cardiomyocytes

Insulin-like growth factor (IGF)-1 activates intracellular signaling pathwa ys and regulates myocardial structure and function. This study used DNA mic roarray to define the effects of IGF-1 on gene expression in cardiomyocytes . Despite DNA microarray becoming a popular tool for profiling gene express ion, the specificity of DNA microarray results is rarely addressed, Our dat a showed that the specificity of a DNA microarray study can be increased by repetitive experiments and by excluding minimally expressed genes, In this study, the false-positive rates were reduced to <0.2%. Future DNA microarr ay studies should incorporate a proper strategy to minimize false-positive results. IGF-1 modulates the expression of genes in 17 functional categorie s, but most genes clustered around the regulation of intracellular signalin g, cell cycle, transcription/translation, cellular respiration and mitochon drial function, cell survival, ion channels and calcium signaling, and humo ral factors. To further explore whether extracellular signal-regulated kina se (ERK) and phosphatidylinositol (PI) 3 kinase specifically regulate diffe rent sets of genes, the effects of IGF-1 were inhibited with PD98059 or LY2 94002, The results showed that the majority of genes regulated by IGF-I req uired activation of both ERK and PI 3 kinase. Thus, PI 3 kinase and ERK coo rdinately mediate the transcriptional regulatory effects of IGF-I in cardia c muscle cells. These findings provide novel insight into how IGF-1 signali ng modulates the programming of cardiac muscle gene expression.