PMID- 24732966
OWN - NLM
STAT- MEDLINE
DCOM- 20150119
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 4
DP  - 2014
TI  - Effects of calorie restriction and diet-induced obesity on murine colon 
      carcinogenesis, growth and inflammatory factors, and microRNA expression.
PG  - e94765
LID - 10.1371/journal.pone.0094765 [doi]
LID - e94765
AB  - Obesity is an established colon cancer risk factor, while preventing or reversing 
      obesity via a calorie restriction (CR) diet regimen decreases colon cancer risk. 
      Unfortunately, the biological mechanisms underlying these associations are poorly 
      understood, hampering development of mechanism-based approaches for preventing 
      obesity-related colon cancer. We tested the hypotheses that diet-induced obesity 
      (DIO) would increase (and CR would decrease) colon tumorigenesis in the mouse 
      azoxymethane (AOM) model. In addition, we established that changes in 
      inflammatory cytokines, growth factors, and microRNAs are associated with these 
      energy balance-colon cancer links, and thus represent mechanism-based targets for 
      colon cancer prevention. Mice were injected with AOM once a week for 5 weeks and 
      randomized to: 1) control diet; 2) 30% CR diet; or 3) DIO diet. Mice were 
      euthanized at week 5 (n = 12/group), 10 (n = 12/group), and 20 (n = 20/group) 
      after the last AOM injection. Colon tumors were counted, and cytokines, 
      insulin-like growth factor 1 (IGF-1), IGF binding protein 3 (IGFBP-3), 
      adipokines, proliferation, apoptosis, and expression of microRNAs (miRs) were 
      measured. The DIO diet regimen induced an obese phenotype ( approximately 36% body fat), while 
      CR induced a lean phenotype ( approximately 14% body fat); controls were intermediate ( approximately 26% 
      body fat). Relative to controls, DIO increased (and CR decreased) the number of 
      colon tumors (p = 0.01), cytokines (p<0.001), IGF-1 (p = 0.01), and proliferation 
      (p<0.001). DIO decreased (and CR increased) IGFBP-3 and apoptosis (p<0.001). miRs 
      including mir-425, mir-196, mir-155, mir-150, mir-351, mir-16, let-7, mir34, and 
      mir-138 were differentially expressed between the dietary groups. We conclude 
      that the enhancing effects of DIO and suppressive effects of CR on colon 
      carcinogenesis are associated with alterations in several biological pathways, 
      including inflammation, IGF-1, and microRNAs.
FAU - Olivo-Marston, Susan E
AU  - Olivo-Marston SE
AD  - Laboratory of Human Carcinogenesis, National Cancer Institute, Center for Cancer 
      Research, National Institutes of Health, Bethesda, Maryland, United States of 
      America; Division of Epidemioogy, The Ohio State University College of Public 
      Health, Columbus, Ohio, United States of America.
FAU - Hursting, Stephen D
AU  - Hursting SD
AD  - Department of Nutritional Sciences, University of Texas-Austin, Austin, Texas, 
      United States of America; Department of Molecular Carcinogenesis, University of 
      Texas-MD Anderson Cancer Center, Smithville, Texas, United States of America.
FAU - Perkins, Susan N
AU  - Perkins SN
AD  - Center for Cancer Training, The National Cancer Institute, National Institutes of 
      Health, Bethesda, Maryland, United States of America.
FAU - Schetter, Aaron
AU  - Schetter A
AD  - Laboratory of Human Carcinogenesis, National Cancer Institute, Center for Cancer 
      Research, National Institutes of Health, Bethesda, Maryland, United States of 
      America.
FAU - Khan, Mohammed
AU  - Khan M
AD  - Laboratory of Human Carcinogenesis, National Cancer Institute, Center for Cancer 
      Research, National Institutes of Health, Bethesda, Maryland, United States of 
      America.
FAU - Croce, Carlo
AU  - Croce C
AD  - Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State 
      University College of Medicine, Columbus, Ohio, United States of America.
FAU - Harris, Curtis C
AU  - Harris CC
AD  - Laboratory of Human Carcinogenesis, National Cancer Institute, Center for Cancer 
      Research, National Institutes of Health, Bethesda, Maryland, United States of 
      America.
FAU - Lavigne, Jackie
AU  - Lavigne J
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 
      Bethesda, Maryland, United States of America.
LA  - eng
GR  - P30 CA016058/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20140414
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Adipokines)
RN  - 0 (Cytokines)
RN  - 0 (Insulin-Like Growth Factor Binding Protein 3)
RN  - 0 (MicroRNAs)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
SB  - IM
MH  - Adipokines/metabolism
MH  - Animals
MH  - Apoptosis
MH  - Body Composition
MH  - Body Weight
MH  - *Caloric Restriction
MH  - Carcinogenesis
MH  - Cell Proliferation
MH  - Colonic Neoplasms/*complications/pathology
MH  - Cytokines/metabolism
MH  - *Diet
MH  - *Gene Expression Regulation, Neoplastic
MH  - Glucose Tolerance Test
MH  - Inflammation/metabolism
MH  - Insulin-Like Growth Factor Binding Protein 3/metabolism
MH  - Insulin-Like Growth Factor I/metabolism
MH  - Male
MH  - Mice
MH  - MicroRNAs/*metabolism
MH  - Obesity/*complications
MH  - Random Allocation
MH  - Risk Factors
PMC - PMC3986228
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/04/16 06:00
MHDA- 2015/01/20 06:00
PMCR- 2014/04/14
CRDT- 2014/04/16 06:00
PHST- 2012/12/20 00:00 [received]
PHST- 2013/05/28 00:00 [accepted]
PHST- 2014/04/16 06:00 [entrez]
PHST- 2014/04/16 06:00 [pubmed]
PHST- 2015/01/20 06:00 [medline]
PHST- 2014/04/14 00:00 [pmc-release]
AID - PONE-D-13-00054 [pii]
AID - 10.1371/journal.pone.0094765 [doi]
PST - epublish
SO  - PLoS One. 2014 Apr 14;9(4):e94765. doi: 10.1371/journal.pone.0094765. eCollection 
      2014.