PMID- 21480390
OWN - NLM
STAT- MEDLINE
DCOM- 20110609
LR  - 20211020
IS  - 1098-2744 (Electronic)
IS  - 0899-1987 (Print)
IS  - 0899-1987 (Linking)
VI  - 50
IP  - 5
DP  - 2011 May
TI  - Energy balance modulates colon tumor growth: Interactive roles of insulin and 
      estrogen.
PG  - 370-82
LID - 10.1002/mc.20720 [doi]
AB  - Obesity increases colorectal cancer (CRC) risk and progression. However, the 
      impact of obesity on CRC in women is dependent on ovarian hormone status. The 
      purpose of this study was to determine the interactive roles of obesity and 
      ovarian hormones on serum markers of inflammation, cell signaling, and 
      transplanted colon tumor growth. Female C57BL/6 mice (6 wk) were either 
      ovariectomized (OVX) or ovaries left intact (nonovariectomized, NOVX) and 
      randomized to receive a (1) control, (2) 30% calorie-restricted (CR), or (3) 
      diet-induced obese (DIO) diet regimen for 20 wk to induce differing levels of 
      adiposity. Serum was collected and inflammatory and metabolic markers were 
      measured using an antibody array (62 proteins) and ELISAs. Mice were 
      subcutaneously injected with syngeneic MC38 colon cancer cells after 20 wk and 
      sacrificed 4 wk later. CR mice had the smallest tumors irrespective of hormone 
      status, whereas the largest tumors were observed in DIO-OVX mice. Glucose 
      tolerance was impaired in OVX mice, being most severe in the DIO-OVX group. 
      Cytokine arrays suggested that in CR animals, inhibition of tumor growth 
      paralleled insulin sensitivity and associated changes in leptin, adiponectin, and 
      IGF-BPs. Conversely, in DIO-OVX animals, tumor growth was associated with insulin 
      and leptin resistance as well as higher levels of pro-inflammatory proteins. In 
      vitro, leptin and adiponectin had no effect, whereas insulin induced MC38 cell 
      proliferation and MAPK activation. Co-treatment with estrogen blocked the 
      stimulatory effects of insulin. Thus, our in vitro and in vivo data indicate 
      female reproductive hormones have a modulating effect on obesity-induced insulin 
      resistance and inflammation, which may directly or indirectly influence CRC 
      progression.
CI  - Copyright (c)2010 Wiley-Liss, Inc.
FAU - Rondini, Elizabeth A
AU  - Rondini EA
AD  - Department of Food Science and Human Nutrition, Michigan State University, East 
      Lansing, Michigan 48824, USA.
FAU - Harvey, Alison E
AU  - Harvey AE
FAU - Steibel, Juan P
AU  - Steibel JP
FAU - Hursting, Stephen D
AU  - Hursting SD
FAU - Fenton, Jenifer I
AU  - Fenton JI
LA  - eng
GR  - P30 ES007784/ES/NIEHS NIH HHS/United States
GR  - P30 ES007784-04/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20101228
PL  - United States
TA  - Mol Carcinog
JT  - Molecular carcinogenesis
JID - 8811105
RN  - 0 (Cytokines)
RN  - 0 (Dietary Fats)
RN  - 0 (Estrogens)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Leptin)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Caloric Restriction
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Colorectal Neoplasms/blood/*metabolism/pathology
MH  - Cytokines/blood
MH  - Dietary Fats/adverse effects
MH  - *Energy Metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Estrogens/*metabolism/pharmacology
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Female
MH  - Hypoglycemic Agents/metabolism/pharmacology
MH  - Insulin/*metabolism/pharmacology
MH  - Leptin/metabolism/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitogen-Activated Protein Kinase Kinases/metabolism
MH  - Neoplasm Transplantation
MH  - Obesity/blood/etiology/metabolism
MH  - Ovariectomy
MH  - Phosphorylation/drug effects
MH  - Random Allocation
PMC - PMC3090729
MID - NIHMS262899
EDAT- 2011/04/12 06:00
MHDA- 2011/06/10 06:00
PMCR- 2012/05/01
CRDT- 2011/04/12 06:00
PHST- 2010/11/05 00:00 [received]
PHST- 2010/11/11 00:00 [accepted]
PHST- 2011/04/12 06:00 [entrez]
PHST- 2011/04/12 06:00 [pubmed]
PHST- 2011/06/10 06:00 [medline]
PHST- 2012/05/01 00:00 [pmc-release]
AID - 10.1002/mc.20720 [doi]
PST - ppublish
SO  - Mol Carcinog. 2011 May;50(5):370-82. doi: 10.1002/mc.20720. Epub 2010 Dec 28.