Uneven distribution of protein kinase C-alpha and -beta isozymes in human sarcomas and carcinomas.
Protein kinase C (PKC) represents a family of structurally related Ser/Tre kinases which are involved in mitogenic signalling and may contribute to human neoplasia. To address this issue, the messenger RNA and protein levels of PKC isoenzymes alpha and beta were analyzed in several human sarcoma- and carcinoma-derived cell lines. Carcinomas contained low or undetectable levels of either PKC-alpha or PKC-beta. Sarcomas exhibited similar or increased PKC expression compared to human diploid fibroblasts. Moreover, sarcoma cell lines expressing one PKC isoform did not contain detectable levels of the other. When PKC was depleted from the tumor cells, we observed that the PKC overexpressing sarcomas had reduced their malignant properties as determined by their ability to grow in semisolid medium. In addition, epidermal growth factor-stimulated and erbB2-transformed fibroblasts exhibited enhanced cell growth in the absence of PKC. We propose a model for the effect of PKC as a negative regulator of proliferation in epithelial cells and a growth promoter in fibroblasts.
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Department of Cell Biology and Genetics, University of Alcalá de Henares, Madrid, Spain.
Issing
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Fleming
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Molloy
C J
CJ
D000595:Amino Acid Sequence; D015152:Blotting, Northern; D002277:Carcinoma / Q000201:enzymology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004848:Epithelium / Q000201:enzymology; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D007527:Isoenzymes / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D011493:Protein Kinase C / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012509:Sarcoma / Q000201:enzymology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D010455:Peptides; D012333:RNA, Messenger; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate