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Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
07:42

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays

Published on: September 19, 2018

Tumor promoters block tyrosine-specific phosphorylation of the epidermal growth factor receptor

B Friedman, A R Frackelton, A H Ross

    Proceedings of the National Academy of Sciences of the United States of America
    |May 1, 1984
    PubMed

    Insights

    Three classes of tumor promoters block epidermal growth factor (EGF) receptor tyrosine phosphorylation in A431 cells. This inhibition correlates with EGF receptor binding, suggesting a role for protein kinase C.

    Area of Science:

    • Cell Biology
    • Molecular Pharmacology
    • Cancer Research

    Background:

    • The epidermal growth factor (EGF) receptor plays a crucial role in cell growth and proliferation.
    • Tyrosine phosphorylation of the EGF receptor is a key signaling event.
    • Tumor promoters are compounds that can initiate or accelerate tumor formation.

    Purpose of the Study:

    • To investigate the effect of different classes of tumor promoters on EGF receptor tyrosine phosphorylation.
    • To determine if tumor promoters affect EGF binding to its receptor.
    • To explore the potential involvement of protein kinase C in these processes.

    Main Methods:

    • Treatment of A431 cells with various tumor promoters and their non-promoting analogs.
    • Measurement of EGF receptor tyrosine phosphorylation levels.
    • Assessment of 125I-labeled EGF binding to A431 cells using Scatchard analysis.

    Main Results:

    • Three distinct classes of tumor promoters (phorbol esters, indole alkaloids, polyacetates) inhibited EGF-stimulated tyrosine phosphorylation of the EGF receptor.
    • Non-tumor-promoting analogs did not affect receptor phosphorylation.
    • Tumor promoters inhibited high-affinity EGF binding, with similar dose-responses to phosphorylation inhibition, while overall EGF binding remained unaffected.

    Conclusions:

    • Tumor promoters modulate both EGF receptor tyrosine phosphorylation and high-affinity EGF binding.
    • The data suggest a common initial mechanism for these effects, potentially involving protein kinase C.
    • This highlights a correlation between EGF receptor modulation and tumor promotion.

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