C-MYC GENE-EXPRESSION IS LOCALIZED TO THE MYOCYTE FOLLOWING HEMODYNAMIC OVERLOAD IN-VIVO

Expression of the proto-oncogene c-myc increases in the hemodynamicall y overloaded heart, but expression by cardiac myocytes has not been sh own. To address this issue, right ventricular overload was induced in cats by pulmonary artery banding. Expression of c-myc and alpha-skelet al actin mRNA were determined by Northern analysis. Immune-reactive My c protein was identified by histochemical staining. Steady state level s of c-myc mRNA peaked within 2 h after banding. Levels of alpha-skele tal actin mRNA were maximally increased 48 h-1 week after banding and were still elevated at 1 month. Prominent staining of myocyte nuclei f or immunoreactive Myc protein was detected 48 h after banding although a few interstitial nuclei were also positive. These studies show that c-myc and alpha-skeletal actin gene expression are upregulated in a l arge animal model of hemodynamic overload. The localization of the imm unoreactive Myc protein to right ventricular myocyte nuclei after pulm onary artery banding supports the hypothesis that c-myc induction is p art of a general response in cardiac hypertrophy that is common to man y mammalian species. (C) 1993 Wiley-Liss, Inc.