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C-myc protooncogene modulates cardiac hypertrophic growth in transgenic mice
1Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Abstract:
Protooncogenes such as c-myc have been implicated in the transduction of growth signals in the cardiac myocyte. We examined whether increases in c-myc expression occur in murine heart in vivo as a generalized response to the pharmacological stimulation of myocyte growth. Both triiodothyronine (T3) and the beta-adrenergic agonist isoproterenol were demonstrated to induce a rapid and transient increase in cardiac c-myc mRNA abundance, which preceded an increase in cardiac mass. We then examined whether myocyte growth could be modulated by selectively altering cardiac c-myc expression. The model system used was a strain of transgenic mice exhibiting a 20-fold increase in cardiac c-myc expression. Although in nontransgenic mice the administration of T3 and isoproterenol resulted in similar increases in cardiac mass, in transgenic mice the degree of myocardial growth induced with T3 was significantly greater than that induced with isoproterenol (P less than 0.001). This study demonstrates that increasing the basal expression of c-myc in cardiac myocytes alters the growth response of the heart in vivo to certain hypertrophic stimuli and implicates the c-myc protooncogene in the transduction of selective hypertrophic growth signals in differentiated cardiac myocytes.
Insights
Protooncogene c-myc expression increases in mouse hearts upon growth stimulation. Altering c-myc levels in cardiac myocytes modifies heart growth responses to specific stimuli, implicating it in signal transduction.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Oncogenes
Background:
- Protooncogenes, like c-myc, play a role in cell growth signaling.
- Cardiac myocytes are specialized cells within the heart muscle.
Purpose of the Study:
- To investigate if c-myc expression increases in the heart in response to growth stimuli.
- To determine if modulating c-myc expression affects cardiac myocyte growth.
Main Methods:
- Used triiodothyronine (T3) and isoproterenol to stimulate cardiac myocyte growth in mice.
- Generated transgenic mice with elevated cardiac c-myc expression.
- Measured c-myc mRNA abundance and cardiac mass.
Main Results:
- T3 and isoproterenol induced a rapid, transient increase in cardiac c-myc mRNA.
- This increase preceded a rise in cardiac mass.
- Transgenic mice with higher c-myc showed a greater growth response to T3 than isoproterenol.
Conclusions:
- Increased basal c-myc expression alters cardiac growth responses to specific hypertrophic stimuli.
- The c-myc protooncogene is involved in transducing selective hypertrophic growth signals in differentiated cardiac myocytes.