Characterization of the E-cadherin-catenin complexes in pancreatic carcinoma cell lines.
E-cadherin and its associated cytoplasmic proteins alpha-, beta-, and gamma-catenins play important roles in cell adhesion and signal transduction, as well as in maintenance of the structural and functional organization of polarized epithelial cells. In this study, the expression, distribution, and complex assembly of catenins with E-cadherin was analysed at the steady state in a panel of human pancreatic adenocarcinoma cell lines (BxPc3, HPAF, T3M4, and PaTuII cell lines). The expression and subcellular distribution were determined by western blotting and immunocytochemistry. Co-immunoprecipitation and cross-linking studies were performed to examine the complex assembly in both Triton X-100 (TX-100)-soluble and -insoluble fractions. In BxPc3 and T3M4 cells, E-cadherin exists in two complexes, one with alpha- and gamma-catenin, and the other with beta-catenin alone. In HPAF cells there are two complexes, one consisting of E-cadherin with alpha- and beta-catenin, and another of E-cadherin with gamma-catenin. In PaTuII cells, there is only a single complex of E-cadherin with alpha-catenin and gamma-catenin. Modification of E-cadherin-catenin complexes in HPAF and PaTuII cells was associated with loss of membranous E-cadherin immunolocalization. The common denominator is impaired beta-catenin association with either E-cadherin (PaTuII) or alpha-catenin (BxPc3 and T3M4). This may suggest the presence of distinct mechanisms that modulate the assembly of each complex, which could disturb the tumour suppressor function of E-cadherin and the catenins.
El-Hariry
I
I
Division of Investigative Science, Imperial College of Science, Technology and Medicine, Hammersmith Campus, Du Cane Road, London W12 0NN, U.K.
Jordinson
M
M
Lemoine
N
N
Pignatelli
M
M
D000230:Adenocarcinoma / Q000737:chemistry*; D015153:Blotting, Western; D015820:Cadherins / Q000032:analysis*; D003598:Cytoskeletal Proteins / Q000032:analysis*; D051180:Desmoplakins; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000032:analysis*; D010190:Pancreatic Neoplasms / Q000737:chemistry*; D011233:Precipitin Tests; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin
C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; C495292:JUP protein, human; D009363:Neoplasm Proteins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin