Cardiac myocyte hypertrophy is associated with c-myc protooncogene expression.
The mechanism of hormonally induced cell hypertrophy is unknown. Stimulation of cardiac myocytes by alpha 1-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 alpha-adrenergic agonist norepinephrine (0.002-20 microM) 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 alpha 1-antagonist terazosin (2 microM) but was not affected by the beta-adrenergic antagonist propranolol (2 microM) and was only slightly (25%) attenuated by the alpha 2-adrenergic antagonist yohimbine (2 microM). 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.
D000818:Animals; D006332:Cardiomegaly / Q000209:etiology* / Q000235:genetics; D002455:Cell Division; D002478:Cells, Cultured; D009638:Norepinephrine / Q000494:pharmacology; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology
D012333:RNA, Messenger; D011942:Receptors, Adrenergic, alpha; D009638:Norepinephrine