PMID- 19138937
OWN - NLM
STAT- MEDLINE
DCOM- 20090305
LR  - 20220321
IS  - 1940-6215 (Electronic)
IS  - 1940-6215 (Linking)
VI  - 1
IP  - 1
DP  - 2008 Jun
TI  - Dietary energy balance modulates signaling through the Akt/mammalian target of 
      rapamycin pathways in multiple epithelial tissues.
PG  - 65-76
LID - 10.1158/1940-6207.CAPR-08-0022 [doi]
AB  - The prevalence of obesity, an established risk factor for several types of 
      cancer, has increased steadily over the past several decades in the United 
      States. New targets and strategies for offsetting the effect of obesity on cancer 
      risk are urgently needed. In the present study, we examined the effect of dietary 
      energy balance manipulation on steady-state signaling in multiple epithelial 
      tissues, with a focus on the Akt and mammalian target of rapamycin (mTOR) 
      pathways. For these experiments, male FVB/N and C57BL/6 and female ICR mice were 
      maintained on a control (10 kcal% fat) diet, a diet-induced obesity (DIO; 60 
      kcal% fat) regimen, or a 30% calorie restriction (CR) regimen for 15 to 17 weeks. 
      Relative to the control group, the DIO regimen increased, whereas CR decreased, 
      circulating insulin-like growth factor-I (IGF-I) as has previously been reported. 
      Western blot analyses showed that the DIO regimen enhanced, whereas CR inhibited, 
      activation of Akt and mTOR, regardless of epithelial tissue or genetic 
      background. In contrast, activation of AMP-activated protein kinase was modulated 
      by dietary energy balance manipulation in the liver but not in the epidermis or 
      dorsolateral prostate. Western blot analyses of epidermal extracts taken from ICR 
      mice also revealed reduced activation of both the IGF-I receptor and epidermal 
      growth factor receptor in CR mice, compared with control mice or mice maintained 
      on the DIO regimen. Taken together, these novel findings suggest that dietary 
      energy balance modulates signaling through cell-surface receptors (i.e., IGF-I 
      receptor and epidermal growth factor receptor), affecting activation of multiple 
      downstream pathways including Akt and mTOR, thus providing important dietary and 
      pharmacologic targets for disrupting the obesity-cancer link.
FAU - Moore, Tricia
AU  - Moore T
AD  - Science Park-Research Division, The University of Texas M. D. Anderson Cancer 
      Center, Smithville, TX 78957, USA.
FAU - Beltran, Linda
AU  - Beltran L
FAU - Carbajal, Steve
AU  - Carbajal S
FAU - Strom, Sara
AU  - Strom S
FAU - Traag, Jeanine
AU  - Traag J
FAU - Hursting, Stephen D
AU  - Hursting SD
FAU - DiGiovanni, John
AU  - DiGiovanni J
LA  - eng
GR  - CA107588/CA/NCI NIH HHS/United States
GR  - CA16672/CA/NCI NIH HHS/United States
GR  - CA37111/CA/NCI NIH HHS/United States
GR  - ES007247/ES/NIEHS NIH HHS/United States
GR  - ES007784/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080331
PL  - United States
TA  - Cancer Prev Res (Phila)
JT  - Cancer prevention research (Philadelphia, Pa.)
JID - 101479409
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
EIN - Cancer Prev Res (Phila Pa). 2009 Nov;2(11):999
MH  - Animals
MH  - Body Fat Distribution
MH  - Body Weight
MH  - *Diet
MH  - Eating/physiology
MH  - Energy Metabolism/*physiology
MH  - Epithelium/*metabolism
MH  - Female
MH  - Homeostasis/physiology
MH  - Insulin-Like Growth Factor I/analysis/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred ICR
MH  - Oncogene Protein v-akt/metabolism/*physiology
MH  - Protein Kinases/metabolism/*physiology
MH  - Signal Transduction/physiology
MH  - TOR Serine-Threonine Kinases
EDAT- 2009/01/14 09:00
MHDA- 2009/03/06 09:00
CRDT- 2009/01/14 09:00
PHST- 2009/01/14 09:00 [entrez]
PHST- 2009/01/14 09:00 [pubmed]
PHST- 2009/03/06 09:00 [medline]
AID - 1940-6207.CAPR-08-0022 [pii]
AID - 10.1158/1940-6207.CAPR-08-0022 [doi]
PST - ppublish
SO  - Cancer Prev Res (Phila). 2008 Jun;1(1):65-76. doi: 
      10.1158/1940-6207.CAPR-08-0022. Epub 2008 Mar 31.