Restoration of E-cadherin/beta-catenin expression in pancreatic cancer cells inhibits growth by induction of apoptosis.
BACKGROUND
beta-Catenin is a component of the E-cadherin/catenin adhesion complex that maintains epithelial cell integrity. We have previously observed decreased beta-catenin expression in both human pancreatic cancer cell lines and primary tumors. To determine the significance of this finding with respect to pancreatic carcinogenesis, this study evaluated the effects of restoring expression of beta-catenin with and without E-cadherin in pancreatic cancer cells.


METHODS
MiaPaca-2 cells were stably transfected with full-length cDNAs for beta-catenin, E-cadherin, or a mutated E-cadherin lacking the beta-catenin-binding domain. Doubly transfected cell clones containing beta-catenin and either E-cadherin or deleted E-cadherin were also selected. Assays for cell adhesion, cell cycle profile, motility, and apoptosis were performed.


RESULTS
Cell clones expressing beta-catenin alone or beta-catenin and deleted E-cadherin did not differ significantly from the parental cell lines in any of the assays performed. In contrast, MiaPaca-2 cell clones expressing both beta-catenin and E-cadherin showed tight adhesion, decreased cell growth, and a significantly increased apoptotic index as compared to the parental line or singly transfected clones.


CONCLUSIONS
MiaPaca-2 cells undergo apoptosis at a significantly increased rate after restoration of the E-cadherin/beta-catenin adhesion complex. This increase in apoptosis is dependent on the ability of E-cadherin to bind beta-catenin. Loss of beta-catenin expression may therefore provide pancreatic cancer cells with a growth advantage that contributes to tumor progression.
Lowy
Andrew M
AM
Division of Surgical Oncology, Department of Surgery, University of Cincinnati College of Medicine, Ohio 45219, USA.
Knight
Joy
J
Groden
Joanna
J
D017209:Apoptosis / Q000502:physiology*; D001943:Breast Neoplasms; D015820:Cadherins / Q000235:genetics*; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010190:Pancreatic Neoplasms; D015534:Trans-Activators / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000502:physiology; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin