Dysregulation of beta-catenin expression correlates with tumor differentiation in pancreatic duct adenocarcinoma.
BACKGROUND
beta-Catenin functions as an integral part of the E-cadherin/catenin adhesion complex to maintain epithelial cell integrity. beta-Catenin also functions as part of the Wnt signal transduction pathway to transmit growth-promoting signals to the nucleus via its interactions with Tcf/Lef transcription factors. Previous reports have demonstrated altered beta-catenin expression in numerous tumor types; however, reports regarding beta-catenin expression in pancreatic cancer have been conflicting.


METHODS
beta-Catenin expression was examined in 10 pancreatic cancer cell lines by Western and Northern analysis and by immunofluorescence. Expression was also examined by immunohistochemistry in 57 primary pancreatic cancers and 7 foci of carcinoma-in-situ.


RESULTS
Reduced expression of beta-catenin was observed in 4 of 10 pancreatic cancer cell lines. Reduced membranous expression was noted in 32 pancreatic cancers (56%) and correlated with loss of tumor differentiation. Nuclear beta-catenin expression was identified in two tumors (4%). beta-Catenin expression was present in all seven foci of carcinoma-in-situ; however, nuclear expression was predominant in four of the seven cases.


CONCLUSIONS
Alterations in beta-catenin expression are common in pancreatic cancer; however, signaling and adhesion functions may be perturbed at different times during tumor progression. Therefore, dysregulation of beta-catenin may contribute to the development and progression of this disease through distinct mechanisms.
Lowy
Andrew M
AM
Department of Surgery, Division of Surgical Oncology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45219-0772, USA. lowyam@healthall.com
Fenoglio-Preiser
Cecilia
C
Kim
On Ja
OJ
Kordich
Jennifer
J
Gomez
Ana
A
Knight
Joy
J
James
Laura
L
Groden
Joanna
J
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000473:pathology*; D002454:Cell Differentiation; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000494:pharmacology; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*; D015398:Signal Transduction; D015534:Trans-Activators / Q000032:analysis / Q000096:biosynthesis* / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin