PMID- 20143392
OWN - NLM
STAT- MEDLINE
DCOM- 20100915
LR  - 20231213
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 127
IP  - 9
DP  - 2010 Nov 1
TI  - Elevated expression of tumor necrosis factor-alpha signaling molecules in colonic 
      tumors of Zucker obese (fa/fa) rats.
PG  - 2042-50
LID - 10.1002/ijc.25232 [doi]
AB  - Zucker obese rats are highly sensitive to colon cancer and possess a plethora of 
      metabolic abnormalities including elevated levels of cytokine tumor necrosis 
      factor-alpha (TNF-alpha). The main objective of this study was to determine if 
      physiologically elevated TNF-alpha affects colonic tumor phenotype with regard to 
      an altered TNF-alpha signaling pathway. Zucker obese (fa/fa, homozygous recessive 
      for dysfunctional leptin receptors), Zucker lean (Fa/fa, Fa/Fa) and 
      Sprague-Dawley (SD) rats were injected twice with azoxymethane (10 mg/kg) over 2 
      weeks. After 30 weeks, the animals were terminated and physiological and tumor 
      parameters were assessed. Obese rats had notably higher body and organ weights as 
      well as plasma TNF-alpha, insulin and leptin levels than lean or SD animals. A 
      100% tumor incidence and significantly higher tumor size, multiplicity and burden 
      were found in obese rats compared to the lean group that had 47.8% tumor 
      incidence. The SD group had the lowest tumor incidence (20.0%). Tumors from obese 
      animals had higher protein levels of TNF-alpha, TNF-alpha-receptor-2 (TNFR2), 
      nuclear transcription factor-kappaB (NF-kappaB) and IkappaB-kinasebeta (IKKbeta) 
      compared to lean animals. In both obese and lean groups, expression levels of 
      these proteins were higher in tumors than in surrounding, normal-appearing 
      colonic mucosae. These findings support an important role for TNF-alpha signaling 
      in tumorigenesis and demonstrate that tumors growing in an obese state had 
      significantly different expression levels of TNFR2 and NF-kappaB, proteins known 
      to play a critical role in growth and survival, than those growing in the lean 
      state. It is concluded that the physiological state of the host intricately 
      affects tumor phenotype.
FAU - Jain, Swati S
AU  - Jain SS
AD  - Department of Human Health and Nutritional Sciences, University of Guelph, 
      Guelph, ON, Canada.
FAU - Bird, Ranjana P
AU  - Bird RP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type II)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - MO0N1J0SEN (Azoxymethane)
SB  - IM
MH  - Animals
MH  - Azoxymethane
MH  - Blood Cell Count
MH  - Colonic Neoplasms/chemically induced/*metabolism
MH  - Female
MH  - NF-kappa B/metabolism
MH  - Obesity/*metabolism
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Rats, Zucker
MH  - Receptors, Tumor Necrosis Factor, Type II/metabolism
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/*metabolism
MH  - NF-kappaB-Inducing Kinase
EDAT- 2010/02/10 06:00
MHDA- 2010/09/17 06:00
CRDT- 2010/02/10 06:00
PHST- 2010/02/10 06:00 [entrez]
PHST- 2010/02/10 06:00 [pubmed]
PHST- 2010/09/17 06:00 [medline]
AID - 10.1002/ijc.25232 [doi]
PST - ppublish
SO  - Int J Cancer. 2010 Nov 1;127(9):2042-50. doi: 10.1002/ijc.25232.