Expression of cadherin-catenin cell adhesion molecules, phosphorylated tyrosine residues and growth factor receptor-tyrosine kinases in gastric cancers.
Tyrosine phosphorylation of beta-catenin, an intracytoplasmic E-cadherin-binding protein, has been shown to disrupt the cadherin-mediated cell adhesion system in vitro. In order to investigate the relationships of expression and tyrosine phosphorylation of cadherin-catenin molecules and expression of growth factor receptor-tyrosine kinase with loose cell-to-cell adhesion, immunohistochemical staining for E-cadherin, alpha- and beta-catenin, phosphorylated tyrosine residues and tyrosine kinase receptors, including c-erbB-2, epidermal growth factor-receptor (EGF-R), c-met and K-sam, in 17 undifferentiated- and 10 differentiated-type human gastric cancers was performed. Loss or reduced expressions of E-cadherin and alpha- and beta-catenin (11, 11, 10 cancers, respectively) were observed in the former, but not the latter. Diffuse cytoplasmic staining of E-cadherin, alpha- and beta-catenin and phosphotyrosine residues was observed frequently in the undifferentiated-type cancers. The cytoplasmic localization of phosphotyrosine residues in undifferentiated-type cancers was correlated significantly with K-sam expression (P < 0.01) and diffuse cytoplasmic staining of E-cadherin (P < 0.05) and beta-catenin (P < 0.05). Expression of K-sam protein was detected significantly more frequently in undifferentiated- (6/17; P < 0.05) than differentiated-type adenocarcinomas whereas the converse applied to c-erbB-2 expression (8/10 of the latter, P < 0.05). Tyrosine phosphorylation of beta-catenin was directly confirmed in the protein extracts of one undifferentiated-type gastric cancer. These data indicate that alteration of tyrosine phosphorylation status associated with K-sam expression may cause the cytoplasmic distribution of cadherin-catenin molecules and loose cell-cell adhesion in undifferentiated-type gastric cancers.
Pathology Division, National Cancer Center Research Institute, Tokyo.
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Akimoto
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Ochiai
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Inomata
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Hirohashi
D015820:Cadherins / Q000096:biosynthesis* / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000096:biosynthesis* / Q000378:metabolism; D013194:Staining and Labeling; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D015534:Trans-Activators; D014443:Tyrosine / Q000378:metabolism*; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins; D017978:Receptors, Growth Factor; D015534:Trans-Activators; D051176:beta Catenin; D019000:Phosphotyrosine; D014443:Tyrosine; D020794:Receptor Protein-Tyrosine Kinases