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.
Metastasis Research Group, University Department of Surgery, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, UK. daviesg11@cf.ac.uk
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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