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PMID: 16902412 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Hypertrophic growth in cardiac myocytes is mediated by Myc through a Cyclin D2-dependent pathway.

The EMBO journal ·Vol. 25 ·No. 16 ·2006-08-23 ·Pages 3869-79

Zhong W, Mao S, Tobis S, Angelis E, Jordan MC, Roos KP, Fishbein MC, de Alborán IM, MacLellan WR

Abstract

c-Myc (Myc) is highly expressed in developing embryos where it regulates body size by controlling proliferation but not cell size. However, Myc is also induced in many postmitotic tissues, including adult myocardium, in response to stress where the predominant form of growth is an increase in cell size (hypertrophy) and not number. The function of Myc induction in this setting is unproven. Therefore, to explore Myc's role in hypertrophic growth, we created mice where Myc can be inducibly inactivated, specifically in adult myocardium. Myc-deficient hearts demonstrated attenuated stress-induced hypertrophic growth, secondary to a reduction in cell growth of individual myocytes. To explore the dependence of Myc-induced cell growth on CycD2, we created bigenic mice where Myc can be selectively activated in CycD2-null adult myocardium. Myc-dependent hypertrophic growth and cell cycle reentry is blocked in CycD2-deficient hearts. However, in contrast to Myc-induced DNA synthesis, hypertrophic growth is independent of CycD2-induced Cdk2 activity. These data suggest that Myc is required for a normal hypertrophic response and that its growth-promoting effects are also mediated through a CycD2-dependent pathway.

MeSH Terms
Animals Apoptosis Cardiomegaly/metabolism,pathology Cell Cycle Cell Enlargement Cell Proliferation Cells, Cultured Cyclin D2 Cyclins/genetics,physiology Isoproterenol/pharmacology Mice Mice, Transgenic Myocardium/metabolism,pathology Myocytes, Cardiac/drug effects,pathology,physiology Proto-Oncogene Proteins c-myc/genetics,physiology
Chemicals
Ccnd2 protein, mouse Cyclin D2 Cyclins Myc protein, mouse Proto-Oncogene Proteins c-myc Isoproterenol
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Zhong Weiguang
The Cardiovascular Research Laboratories, Department of Medicine, UCLA School of Medicine, Los Angeles, California, USA.
Mao Songyan
Tobis Scott
Angelis Ekaterini
Jordan Maria C
Roos Kenneth P
Fishbein Michael C
de Alborán Ignacio Moreno
MacLellan W Robb
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7601252
Published
2006-08-23
Epub
2006-00-10
Pages
3869-79
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1553193
Subset
IM
Grants
NHLBI NIH HHS · R01 HL070748 · United States
NHLBI NIH HHS · R01 HL 70748 · United States
External Links
PubMed source DOI: 10.1038/sj.emboj.7601252 PMC Full Text View journal details
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