C/EBPbeta regulates body composition, energy balance-related hormones and tumor growth.
The prevalence of obesity, an established epidemiologic risk factor for many chronic diseases including cancer, has been steadily increasing in the US over several decades. The mechanisms used to regulate energy balance and adiposity and the relationship of these factors to cancer are not completely understood. Here we have used knockout mice to examine the roles of the transcription factors CCAAT/enhancer-binding protein (C/EBP) beta and C/EBPdelta in regulating body composition and systemic levels of hormones such as insulin-like growth factor-1 (IGF-1), leptin and insulin that mediate energy balance. Dual-energy X-ray absorptiometry showed that C/EBPbeta, either directly or indirectly, modulated body weight, fat content and bone density in both males and females, while the effect of C/EBPdelta was minor and only affected adiposity and body weight in female animals. Levels of IGF-1, leptin and insulin in the serum were decreased in both male and female C/EBPbeta(-/-) mice, and C/EBPbeta was associated with their promoters in vivo. Moreover, colon adenocarcinoma cells displayed reduced tumorigenic potential when transplanted into C/EBPbeta-deficient animals, especially males. Thus, C/EBPbeta contributes to endocrine expression of IGF-1, leptin and insulin, which modulate energy balance and can contribute to cancer progression by creating a favorable environment for tumor cell proliferation and survival.
Staiger
Jennifer
J
Basic Research Laboratory, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, MD 21702-1201, USA.
Lueben
Mary J
MJ
Berrigan
David
D
Malik
Radek
R
Perkins
Susan N
SN
Hursting
Stephen D
SD
Johnson
Peter F
PF
D000230:Adenocarcinoma / Q000473:pathology; D000273:Adipose Tissue / Q000502:physiology; D000818:Animals; D001823:Body Composition / Q000502:physiology*; D001835:Body Weight; D015519:Bone Density; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D002455:Cell Division / Q000235:genetics; D003110:Colonic Neoplasms / Q000473:pathology; D005260:Female; D007328:Insulin / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D020738:Leptin / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009369:Neoplasms / Q000453:epidemiology*; D009765:Obesity / Q000150:complications / Q000235:genetics / Q000503:physiopathology*
D022782:CCAAT-Enhancer-Binding Protein-beta; D007328:Insulin; D020738:Leptin; D051743:CCAAT-Enhancer-Binding Protein-delta; D007334:Insulin-Like Growth Factor I