Chemical reverse transformation of CHO-K1 cells induces changes in expression of a candidate tumour suppressor and of a gene not previously characterised as transformation related

CZ Bachrati, Stephen Downes, I Rasko

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    Abstract

    Chemical reverse transformation of CHO-K1 and other cells is a well-established phenomenon, in which oncogenically transformed cells re-acquire fibroblastoid morphology, contact inhibition and anchorage-dependent growth, in response to cyclic AMP and other agents. A limited number of changes in gene transcription and enzyme activity have been demonstrated to coincide with these morphological and physiological changes. We have used a partial differential display to identify four genes that are transcriptionally modulated in reverse transformation. One of these, encoding ribosomal protein S18, is transcriptionally suppressed, probably as a result of the detransforming process. Three others are transcriptionally activated. One has homology to NADH-ubiquinone oxidoreductase chain 4 protein, and is also probably changed as a result of the detransforming process. Another is homologous to a human sequence which encodes a 27 kDa protein, p27(BBP/eIF6), that is involved in the biogenesis of 60S ribosomal subunit, and in cell lines of epithelial origin binds to beta integrin. This has not previously been described as transformation-related, and could have a causative role in reverse transformation. The third has homology, with transcriptional or processing variations, to a human genomic sequence, a positional candidate for a tumour suppressor gene, encoding the Krit1 protein which interacts with the Ras-family GTPase Krev-1.
    LanguageEnglish
    Pages561-566
    JournalEuropean Journal of Cell Biology
    Volume78
    Issue number8
    Publication statusPublished - Aug 1999

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    CHO Cells
    Tumor Suppressor Genes
    Eukaryotic Large Ribosome Subunits
    Integrin beta Chains
    Contact Inhibition
    Electron Transport Complex I
    ras Proteins
    Proteins
    Cyclic AMP
    Genes
    Cell Line
    Enzymes
    Growth

    Cite this

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    title = "Chemical reverse transformation of CHO-K1 cells induces changes in expression of a candidate tumour suppressor and of a gene not previously characterised as transformation related",
    abstract = "Chemical reverse transformation of CHO-K1 and other cells is a well-established phenomenon, in which oncogenically transformed cells re-acquire fibroblastoid morphology, contact inhibition and anchorage-dependent growth, in response to cyclic AMP and other agents. A limited number of changes in gene transcription and enzyme activity have been demonstrated to coincide with these morphological and physiological changes. We have used a partial differential display to identify four genes that are transcriptionally modulated in reverse transformation. One of these, encoding ribosomal protein S18, is transcriptionally suppressed, probably as a result of the detransforming process. Three others are transcriptionally activated. One has homology to NADH-ubiquinone oxidoreductase chain 4 protein, and is also probably changed as a result of the detransforming process. Another is homologous to a human sequence which encodes a 27 kDa protein, p27(BBP/eIF6), that is involved in the biogenesis of 60S ribosomal subunit, and in cell lines of epithelial origin binds to beta integrin. This has not previously been described as transformation-related, and could have a causative role in reverse transformation. The third has homology, with transcriptional or processing variations, to a human genomic sequence, a positional candidate for a tumour suppressor gene, encoding the Krit1 protein which interacts with the Ras-family GTPase Krev-1.",
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    AU - Downes, Stephen

    AU - Rasko, I

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    N2 - Chemical reverse transformation of CHO-K1 and other cells is a well-established phenomenon, in which oncogenically transformed cells re-acquire fibroblastoid morphology, contact inhibition and anchorage-dependent growth, in response to cyclic AMP and other agents. A limited number of changes in gene transcription and enzyme activity have been demonstrated to coincide with these morphological and physiological changes. We have used a partial differential display to identify four genes that are transcriptionally modulated in reverse transformation. One of these, encoding ribosomal protein S18, is transcriptionally suppressed, probably as a result of the detransforming process. Three others are transcriptionally activated. One has homology to NADH-ubiquinone oxidoreductase chain 4 protein, and is also probably changed as a result of the detransforming process. Another is homologous to a human sequence which encodes a 27 kDa protein, p27(BBP/eIF6), that is involved in the biogenesis of 60S ribosomal subunit, and in cell lines of epithelial origin binds to beta integrin. This has not previously been described as transformation-related, and could have a causative role in reverse transformation. The third has homology, with transcriptional or processing variations, to a human genomic sequence, a positional candidate for a tumour suppressor gene, encoding the Krit1 protein which interacts with the Ras-family GTPase Krev-1.

    AB - Chemical reverse transformation of CHO-K1 and other cells is a well-established phenomenon, in which oncogenically transformed cells re-acquire fibroblastoid morphology, contact inhibition and anchorage-dependent growth, in response to cyclic AMP and other agents. A limited number of changes in gene transcription and enzyme activity have been demonstrated to coincide with these morphological and physiological changes. We have used a partial differential display to identify four genes that are transcriptionally modulated in reverse transformation. One of these, encoding ribosomal protein S18, is transcriptionally suppressed, probably as a result of the detransforming process. Three others are transcriptionally activated. One has homology to NADH-ubiquinone oxidoreductase chain 4 protein, and is also probably changed as a result of the detransforming process. Another is homologous to a human sequence which encodes a 27 kDa protein, p27(BBP/eIF6), that is involved in the biogenesis of 60S ribosomal subunit, and in cell lines of epithelial origin binds to beta integrin. This has not previously been described as transformation-related, and could have a causative role in reverse transformation. The third has homology, with transcriptional or processing variations, to a human genomic sequence, a positional candidate for a tumour suppressor gene, encoding the Krit1 protein which interacts with the Ras-family GTPase Krev-1.

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