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Relation of epidermal growth factor receptor concentration to growth of human epidermoid carcinoma A431 cells
Abstract:
The relation between the concentration of epidermal growth factor (EGF) receptor/kinase and effects of EGF on cell proliferation has been studied using variant A431 cells and antagonist anti-EGF receptor monoclonal antibodies. Clonal A431 cell variants selected for escape from the EGF-mediated growth inhibition of parental A431 cells all have reduced concentrations of EGF receptor/kinase; Harvey sarcoma virus-transformed A431 cells, which have escaped from EGF-mediated growth inhibition, also have reduced EGF receptors. Three clonal variants which have reacquired EGF-mediated growth inhibition have 2- to 4-fold more EGF receptor than their respective parent variant. A biphasic response with stimulation at low and inhibition at high concentrations of EGF was especially evident in revertants of clone 29. Three separate antagonist monoclonal anti-EGF receptor antibodies block the growth inhibitory effects of EGF and uncover EGF-mediated growth stimulation. These studies indicate that in A431 cell variants a continuum of ligand-activated EGF receptors determines proliferative responses from low concentrations of active receptors under basal conditions to intermediate concentrations causing growth stimulation to high concentrations, causing inhibition of cell proliferation.
Insights
Epidermal Growth Factor (EGF) receptor concentration dictates cell proliferation. Reduced EGF receptor levels can lead to growth escape, while increased levels restore EGF-mediated growth inhibition in A431 cell variants.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Epidermal Growth Factor (EGF) receptor signaling is crucial for cell growth and proliferation.
- Dysregulation of EGF receptor activity is implicated in various cancers.
- Understanding the dose-dependent effects of EGF is vital for therapeutic strategies.
Purpose of the Study:
- To investigate the relationship between epidermal growth factor (EGF) receptor/kinase concentration and EGF's effects on cell proliferation.
- To analyze how variations in EGF receptor levels influence A431 cell growth responses to EGF.
- To explore the role of antagonist monoclonal antibodies in modulating EGF-mediated cellular effects.
Main Methods:
- Utilized A431 cell variants with differing EGF receptor/kinase concentrations.
- Studied EGF-mediated growth inhibition and stimulation in these variants.
- Employed antagonist monoclonal anti-EGF receptor antibodies to block receptor activity.
Main Results:
- A431 cell variants escaping EGF-mediated growth inhibition exhibited reduced EGF receptor/kinase concentrations.
- Revertant variants regaining growth inhibition showed a 2- to 4-fold increase in EGF receptor levels.
- EGF demonstrated a biphasic response: stimulation at low concentrations and inhibition at high concentrations.
- Monoclonal antibodies against the EGF receptor blocked growth inhibition and revealed growth stimulation.
Conclusions:
- The concentration of ligand-activated EGF receptors determines A431 cell proliferative responses.
- A continuum exists from basal conditions to growth stimulation and inhibition based on EGF receptor activity.
- EGF receptor levels are critical modulators of cell proliferation in response to EGF.