PMID- 23466464
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20130308
LR  - 20211021
IS  - 2155-384X (Print)
IS  - 2155-384X (Electronic)
IS  - 2155-384X (Linking)
VI  - 4
IP  - 3
DP  - 2013 Mar 7
TI  - Insulin/Insulin-Like Growth Factor-1 Pathway in Barrett's Carcinogenesis.
PG  - e31
LID - 10.1038/ctg.2013.2 [doi]
AB  - OBJECTIVES: Obesity-associated carcinogenesis is postulated to be mediated 
      through the proliferative actions of insulin and the insulin-like growth factor 
      (IGF) family. The aim of this study was to determine whether the insulin/IGF-1 
      pathway is involved in the sequential progression from metaplastic Barrett's 
      esophagus (BE) to dysplasia to esophageal adenocarcinoma (EAC). METHODS: Fasting 
      serum levels of insulin, glucose, IGF-1, insulin growth factor binding protein-1 
      (IGFBP1), and IGFBP3 were measured in 44 non-dysplastic, 9 low-grade dysplasia 
      (LGD), 12 high-grade dysplasia (HGD), and 10 EAC subjects. Immunohistochemistry 
      was performed on paraffin-embedded tissue derived from BE cases using rabbit 
      monoclonal antibodies to p-mammalian target of rapamycin (mTOR) and p-AKT, mouse 
      monoclonal antibody to Ki-67, and rabbit polyclonal antibody to p-insulin 
      receptor substrate 1 (IRS1). RESULTS: Nineteen of 44 (43.2%) BE, 5/9 (55%) LGD, 
      8/12 (66.7%) HGD and EAC 7/10 (70%) cases showed strong staining for p-IRS1. A 
      significantly higher proportion of HGD/EAC subjects showed p-IRS1 staining when 
      compared with BE/LGD subjects, 63.6% vs. 41.5%, P<0.05. p-IRS1 immunostaining was 
      moderately correlated with strong immunostaining of the downstream mediators 
      p-AKT and p-mTOR (Spearman correlation coefficient=0.167 and 0.27 for 
      p-IRS1/p-AKT and for p-IRS1/p-mTOR, respectively) and the proliferation marker 
      Ki-67 (Spearman correlation coefficient=0.20, P=0.09). However, systemic levels 
      of insulin, IGF-1, or IGF-2 were not associated with tissue immunostaining of 
      p-IRS1. CONCLUSIONS: Activation of the insulin/IGF-1 pathway in BE may be 
      associated with cellular proliferation and appears to have a role in the 
      progression from metaplasia to cancer. The activation of the insulin/IGF-1 
      pathway at the tissue level is likely complex and does not have a simple 
      association with systemic measures of insulin or IGF-1.
FAU - Greer, K B
AU  - Greer KB
AD  - Division of Gastroenterology and Liver Disease, University Hospitals of 
      Cleveland, Cleveland, Ohio, USA.
FAU - Kresak, A
AU  - Kresak A
FAU - Bednarchik, B
AU  - Bednarchik B
FAU - Dawson, D
AU  - Dawson D
FAU - Li, L
AU  - Li L
FAU - Chak, A
AU  - Chak A
FAU - Willis, J
AU  - Willis J
LA  - eng
GR  - U54 CA163060/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20130307
PL  - United States
TA  - Clin Transl Gastroenterol
JT  - Clinical and translational gastroenterology
JID - 101532142
PMC - PMC3615698
EDAT- 2013/03/08 06:00
MHDA- 2013/03/08 06:01
PMCR- 2013/03/01
CRDT- 2013/03/08 06:00
PHST- 2013/03/08 06:00 [entrez]
PHST- 2013/03/08 06:00 [pubmed]
PHST- 2013/03/08 06:01 [medline]
PHST- 2013/03/01 00:00 [pmc-release]
AID - ctg20132 [pii]
AID - 10.1038/ctg.2013.2 [doi]
PST - epublish
SO  - Clin Transl Gastroenterol. 2013 Mar 7;4(3):e31. doi: 10.1038/ctg.2013.2.