The interaction between beta-catenin, GSK3beta and APC after motogen induced cell-cell dissociation, and their involvement in signal transduction pathways in prostate cancer.
The effect of HGF/SF was examined on the interactions between APC, GSK3beta and beta-catenin in prostate cancer cells LNCapFGC (E-cadherin positive) and PC-3 (E-cadherin negative). Using immunoprecipitation, APC was found to be co-precipitated with either GSK3beta or beta-catenin in both cell lines. Stimulation with HGF/SF showed no change in the co-precipitation status of these protein molecules. In contrast, co-precipitation between GSK3beta and beta-catenin was only observed in LNCapFGC cells, and increased upon continued exposure to the motogen HGF/SF. Furthermore, using immunofluorescence, stimulation with HGF/SF was found to increase the level of co-localised cytoplasmic staining between beta-catenin and GSK3beta, in prostate cancer cells. RT-PCR revealed that there were no mutations within the binding regions between beta-catenin and GSK3beta. It is concluded, that uncomplexed cytoplasmic pools of beta-catenin associate more readily with the Axin complex in the absence of E-cadherin. Whereas, in the presence of E-cadherin, beta-catenin is stabilised by forming tight cell-cell contacts which may influence the invasive potential of cancer cells.
Davies
G
G
Metastasis Research Group, University Department of Surgery, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, UK. daviesg11@cf.ac.uk
Jiang
W G
WG
Mason
M D
MD
D025601:Adenomatous Polyposis Coli Protein; D015820:Cadherins / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D038362:Glycogen Synthase Kinase 3; D006801:Humans; D008297:Male; D011233:Precipitin Tests; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D051176:beta Catenin
D025601:Adenomatous Polyposis Coli Protein; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D015534:Trans-Activators; D051176:beta Catenin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3