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.