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ADP activates protooncogene expression in renal epithelial cells.

S Kartha, V P Sukhatme, F G Toback

    The American Journal of Physiology
    |June 1, 1987
    PubMed
    Summary

    Adenosine diphosphate (ADP) stimulates kidney cell growth by activating protooncogenes like c-Ha-ras and c-myc. This protooncogene activation precedes DNA synthesis, suggesting a key role in cell proliferation.

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    Area of Science:

    • Cell Biology
    • Molecular Biology
    • Biochemistry

    Background:

    • Purine nucleotides, especially adenosine diphosphate (ADP), are potent mitogens for monkey kidney epithelial cells (BSC-1 line).
    • The precise molecular mechanisms underlying ADP's mitogenic effects on renal cells are not fully understood.
    • Protooncogenes play critical roles in cell growth and differentiation.

    Purpose of the Study:

    • To investigate if ADP-induced DNA synthesis in renal epithelial cells is mediated by protooncogene activation.
    • To elucidate the temporal relationship between ADP stimulation, protooncogene expression, and DNA synthesis.

    Main Methods:

    • Culturing BSC-1 monkey kidney epithelial cells.
    • Stimulating quiescent cells with ADP.
    • Quantifying gene expression of c-Ha-ras, c-myc, transferrin receptor, and gamma-actin using transcript analysis.
    • Measuring DNA synthesis initiation.

    Main Results:

    • ADP significantly stimulated the expression of c-Ha-ras protooncogene transcripts (fourfold increase).
    • c-myc protooncogene expression was induced by ADP, peaking at 1 hour.
    • c-Ha-ras and transferrin receptor gene expression peaked at 12 hours, preceding DNA synthesis.
    • Gamma-actin mRNA levels remained unchanged, indicating specific gene regulation.

    Conclusions:

    • Exogenous ADP acts as a mitogen by activating protooncogenes (c-Ha-ras, c-myc) in renal epithelial cells.
    • Protooncogene expression is an early event, occurring before the initiation of DNA synthesis.
    • These findings suggest that ADP's physiological effects may be mediated through protooncogene-encoded proteins.

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