Key result
IGF-1 modulates gene expression in cardiomyocytes via coordinate activation of ERK and PI 3 kinase pathways, with microarray false-positive rates reduced to <0.2% using a repetitive experiment strategy.
PI 3 kinase and ERK coordinately mediate the transcriptional regulatory effects of IGF-1 in cardiac muscle cells, providing insight into myocardial gene expression programming.
Hypothesis-generating for IGF-1 effects on cardiac transcription; leaves open translation to human myocardial remodeling.
Insulin-like growth factor (IGF)-1 activates intracellular signaling pathways and regulates myocardial structure and function. This study used DNA microarray to define the effects of IGF-1 on gene expression in cardiomyocytes. Despite DNA microarray becoming a popular tool for profiling gene expression, the specificity of DNA microarray results is rarely addressed. Our data 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 microarray studies should incorporate a proper strategy to minimize false-positive results. IGF-1 modulates the expression of genes in 17 functional categories, but most genes clustered around the regulation of intracellular signaling, cell cycle, transcription/translation, cellular respiration and mitochondrial function, cell survival, ion channels and calcium signaling, and humoral factors. To further explore whether extracellular signal-regulated kinase (ERK) and phosphatidylinositol (PI) 3 kinase specifically regulate different sets of genes, the effects of IGF-1 were inhibited with PD98059 or LY294002. The results showed that the majority of genes regulated by IGF-1 required activation of both ERK and PI 3 kinase. Thus, PI 3 kinase and ERK coordinately mediate the transcriptional regulatory effects of IGF-1 in cardiac muscle cells. These findings provide novel insight into how IGF-1 signaling modulates the programming of cardiac muscle gene expression.
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Liu et al. (2001) studied Cardiomyocytes (in vitro). Insulin-like growth factor-1 (IGF-1) vs. Inhibitors (PD98059 or LY294002) was evaluated on Gene expression profile and false-positive rate of DNA microarray. IGF-1 modulates gene expression in cardiomyocytes via coordinate activation of ERK and PI 3 kinase pathways, with microarray false-positive rates reduced to <0.2% using a repetitive experiment strategy.
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