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Aberrant Wnt/β-Catenin Signaling in Pancreatic Adenocarcinoma
- Source :
- Neoplasia: An International Journal for Oncology Research, Vol 8, Iss 4, Pp 279-289 (2006)
- Publication Year :
- 2006
- Publisher :
- Elsevier, 2006.
-
Abstract
- Wnt/β-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/β-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 β-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 β-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-β-catenin. Electrophoretic mobility shift assay demonstrated β-cateninT-cell factor binding in tumors only. Adenomatous polyposis coli and axin, which are both negative regulators, remained unchanged. Unexpectedly, total glycogen synthase kinase-3β protein was elevated in these tumors. Elevated levels of E-cadherin were also observed, although E-cadherin-β-catenin association in tumors remained unaffected. Thus, Wnt/β-catenin activation was observed in 65% of pancreatic adenocarcinomas, independently of β-catenin gene mutations in most tumors.
Details
- Language :
- English
- ISSN :
- 14765586 and 15228002
- Volume :
- 8
- Issue :
- 4
- Database :
- Directory of Open Access Journals
- Journal :
- Neoplasia: An International Journal for Oncology Research
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.49b82f33371f448bb61f78cb09a9c369
- Document Type :
- article
- Full Text :
- https://doi.org/10.1593/neo.05607