Abstract
Signet-ring cell carcinomas are malignant dedifferentiated carcinomas, which are frequently found in the stomach. We previously demonstrated that a 200 kDa protein is often constitutively phosphorylated on tyrosine and bound to phosphatidylinositol 3-kinase (PI3-kinase) in signet-ring cell carcinoma cells. In this study, we purified the 200 kDa protein from an extract of NUGC-4 cells, a cell line of signet-ring cell carcinoma, and identified it as ErbB3. ErbB3 was found to be phosphorylated selectively in dedifferentiated adenocarcinoma cell lines among various gastric cancer cell lines. Expression of a constitutively active chimeric receptor consisting of ErbB2 and ErbB3 in HCC2998 cells, a highly differentiated adenocarcinoma cell line, revealed that the signaling triggered by phosphorylation of ErbB3 was important for dedifferentiated phenotypes such as loss of cell-cell interaction and high expression of MUC1/DF3 antigen, a marker of the malignant tumors. Taken together, activation of ErbB3 pathway may contribute to the development of dedifferentiated carcinomas.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / enzymology*
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Adenocarcinoma / pathology
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Amino Acid Motifs
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Amino Acid Sequence
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Antigens, Neoplasm / biosynthesis
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Antigens, Neoplasm / genetics
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Carcinoma, Signet Ring Cell / enzymology*
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Carcinoma, Signet Ring Cell / pathology
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Cell Differentiation
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Cell Polarity
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Colonic Neoplasms / enzymology
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Colonic Neoplasms / pathology
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Enzyme Activation
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Gene Expression Regulation, Neoplastic
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Genes, erbB
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Genes, erbB-2
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Humans
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Molecular Sequence Data
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Mucin-1 / biosynthesis
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Mucin-1 / genetics
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Neoplasm Proteins / isolation & purification
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Neoplasm Proteins / physiology*
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Phenotype
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Phosphatidylinositol 3-Kinases / physiology*
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Phosphorylation
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Protein Processing, Post-Translational
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Receptor, ErbB-2 / genetics
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Receptor, ErbB-2 / physiology
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Receptor, ErbB-3 / isolation & purification
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Receptor, ErbB-3 / physiology*
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Recombinant Fusion Proteins / physiology
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Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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Stomach Neoplasms / enzymology*
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Stomach Neoplasms / pathology
Substances
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Antigens, Neoplasm
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Mucin-1
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Neoplasm Proteins
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Recombinant Fusion Proteins
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Phosphatidylinositol 3-Kinases
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Receptor, ErbB-2
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Receptor, ErbB-3