Cardiac Myocyte Hypertrophy is Associated with c-myc Protooncogene Expression

The mechanism of hormonally induced cell hypertrophy is unknown. Stimulation of cardiac myocytes by α1-adrenergic agents, phorbol esters, and serum induces an increase in the cell size of nondividing cardiac myocytes in primary culture. Expression of the c-myc gene, known to be increased in growth factor-induced cell division, was studied in this model of cell hypertrophy. The α -adrenergic agonist norepinephrine (0.002-20 μ M) increased levels of c-myc-encoded mRNA to 10-fold over control levels. This increase was detectable at 30 min, peaked at 2 hr, and returned to baseline by 6 hr after stimulation. The norepinephrine response was abolished by the α1-antagonist terazosin (2 μ M) but was not affected by the β -adrenergic antagonist propranolol (2 μ M) and was only slightly (25%) attenuated by the α2-adrenergic antagonist yohimbine (2 μ M). Serum and the phorbol ester tumor promoter phorbol 12-myristate 13-acetate also enhanced c-myc expression in cardiac myocyte cultures. These findings show that the induction of cardiac myocyte hypertrophy is associated with enhanced expression of the c-myc gene and suggest that hormonally induced cell hypertrophy and cell division share common mechanistic pathways.