c-Myc regulates mammalian body size by controlling cell number but not cell size.
Overexpression of the proto-oncogene c-myc has been implicated in the genesis of diverse human tumours. c-Myc seems to regulate diverse biological processes, but its role in tumorigenesis and normal physiology remains enigmatic. Here we report the generation of an allelic series of mice in which c-myc expression is incrementally reduced to zero. Fibroblasts from these mice show reduced proliferation and after complete loss of c-Myc function they exit the cell cycle. We show that Myc activity is not needed for cellular growth but does determine the percentage of activated T cells that re-enter the cell cycle. In vivo, reduction of c-Myc levels results in reduced body mass owing to multiorgan hypoplasia, in contrast to Drosophila c-myc mutants, which are smaller as a result of hypotrophy. We find that c-myc substitutes for c-myc in fibroblasts, indicating they have similar biological activities. This suggests there may be fundamental differences in the mechanisms by which mammals and insects control body size. We propose that in mammals c-Myc controls the decision to divide or not to divide and thereby functions as a crucial mediator of signals that determine organ and body size.
Trumpp
A
A
Swiss Institute for Experimental Cancer Research (ISREC), Ch. des Boveresses 155, CH-1066 Epalinges, Switzerland. Andreas.Trumpp@isrec.unil.ch
Refaeli
Y
Y
Oskarsson
T
T
Gasser
S
S
Murphy
M
M
Martin
G R
GR
Bishop
J M
JM
D000818:Animals; D001824:Body Constitution / Q000235:genetics; D002452:Cell Count; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D048429:Cell Size; D002478:Cells, Cultured; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004330:Drosophila; D004622:Embryo, Mammalian / Q000166:cytology; D004625:Embryo, Nonmammalian; D005347:Fibroblasts; D018390:Gene Targeting; D018816:Genes, cdc; D016259:Genes, myc / Q000502:physiology*; D051379:Mice; D000090063:Proto-Oncogene Mas; D013045:Species Specificity; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27