Carcinogenesis Advance Access originally published online on December 4, 2008
Carcinogenesis 2009 30(5):832-840; doi:10.1093/carcin/bgn273
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C/EBPβ regulates body composition, energy balance-related hormones and tumor growth
1 Basic Research Laboratory, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, MD 21702-1201, USA
2 Department of Science, Mount St Mary’s University, Emmitsburg, MD 21727, USA
3 Applied Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD 20892, USA
4 Department of Human Ecology, University of Texas at Austin, Austin, TX 78712, USA
5 Present address: Department of Epigenetic Regulations, Institute of Molecular Genetics AS CR, Videnska 1083, CZ-142 20 Prague 4, Czech Republic
* To whom correspondence should be addressed. Tel: +1 301 846 1627; Fax: +1 301 846 5991; Email: johnsopf{at}ncifcrf.gov
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) β and C/EBP
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/EBPβ, either directly or indirectly, modulated body weight, fat content and bone density in both males and females, while the effect of C/EBP 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/EBPβ–/– mice, and C/EBPβ was associated with their promoters in vivo. Moreover, colon adenocarcinoma cells displayed reduced tumorigenic potential when transplanted into C/EBPβ-deficient animals, especially males. Thus, C/EBPβ 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.
Abbreviations: BMD, bone mineral density; C/EBP, CCAAT/enhancer-binding protein; ChIP, chromatin immunoprecipitation; HSD, honestly significant differences; IGF-1, insulin-like growth factor-1; IL, interleukin
Received July 1, 2008; revised October 27, 2008; accepted November 26, 2008.