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PMID: 16756720 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Aberrant Wnt/beta-catenin signaling in pancreatic adenocarcinoma.

Neoplasia (New York, N.Y.) ·Vol. 8 ·No. 4 ·2006-04-00 ·Pages 279-89

Zeng G, Germinaro M, Micsenyi A, Monga NK, Bell A, Sood A, Malhotra V, Sood N, Midda V, Monga DK, Kokkinakis DM, Monga SP

Abstract

Wnt/beta-catenin signaling plays an important role in normal development. However, its aberrant activation is associated with several cancers. The aim of this study is to examine the Wnt/beta-catenin pathway in patients with advanced pancreatic adenocarcinoma (n = 31). Paraffin sections from tumors (n = 16) and normal pancreata (n = 3) were used to determine the localization of beta-catenin. An additional 15 frozen tumors, adjacent normal pancreata (n = 5), or normal pancreata (n = 4) were utilized for protein isolation. Tumors were also examined for mutations in exon 3 of the CTNNB1 gene. More than 65% of the tumors showed an increase in total beta-catenin, consistent with its enhanced membranous, cytoplasmic, and nuclear localization, but only two showed mutations in CTNNB1. The majority of the remaining tumors demonstrated concurrent increases in Wnt-1 and frizzled-2 (positive regulators) and a decrease in Ser45/Thr41-phospho-beta-catenin. Electrophoretic mobility shift assay demonstrated beta-catenin-T-cell factor binding in tumors only. Adenomatous polyposis coli and axin, which are both negative regulators, remained unchanged. Unexpectedly, total glycogen synthase kinase-3beta protein was elevated in these tumors. Elevated levels of E-cadherin were also observed, although E-cadherin-beta-catenin association in tumors remained unaffected. Thus, Wnt/beta-catenin activation was observed in 65% of pancreatic adenocarcinomas, independently of beta-catenin gene mutations in most tumors.

MeSH Terms
Adenocarcinoma/metabolism Adult Aged Aged, 80 and over DNA Mutational Analysis/methods Female Gene Expression Regulation, Neoplastic Humans Male Middle Aged Pancreatic Neoplasms/metabolism Wnt Proteins/metabolism beta Catenin/metabolism
Chemicals
Wnt Proteins beta Catenin
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Zeng Gang
Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Germinaro Matt
Micsenyi Amanda
Monga Navjot K
Bell Aaron
Sood Ajit
Malhotra Vanita
Sood Neena
Midda Vandana
Monga Dulabh K
Kokkinakis Demetrius M
Monga Satdarshan P S
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Article Info
Journal
Neoplasia (New York, N.Y.)
Abbr.
Neoplasia
ISSN
1476-5586
DOI
10.1593/neo.05607
Published
2006-04-00
Pages
279-89
Language
English
Region
United States
NLM ID
100886622
PMCID
PMC1600679
Subset
IM
Grants
NIDDK NIH HHS · R01 DK062277 · United States
NIDDK NIH HHS · 1R01DK62277 · United States
External Links
PubMed source DOI: 10.1593/neo.05607 PMC Full Text View journal details
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