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Down-modulation of EGF receptors in cells transformed by the src oncogene
Abstract:
The effects of src oncogene expression on epidermal growth factor (EGF) receptors have been investigated in mouse 3T3 and rat-1 fibroblasts. Transformation of both cell types with src resulted in marked reductions in cellular EGF receptor levels, as assayed by either 125I-EGF binding or immunoprecipitation of receptor protein from radiolabeled cell lysates. In contrast to cells transformed by other types of retroviral oncogenes, the loss of EGF receptors in the src-transformed cells did not appear to be due to secreted transforming growth factor-alpha (TGF-alpha), since such factors were undetectable in culture fluids from the src-transformed cells. By several criteria of transformation, an EGF-receptorless cell line infected with src was shown to be transformed, suggesting that EGF receptors themselves are not obligatory to the src transformation process. We suggest that pp60src down-modulates EGF receptors by an intracellular mechanism and that the loss of the receptors is symptomatic of more general effects of pp60src on the machinery of growth regulation.
Insights
The src oncogene reduces epidermal growth factor (EGF) receptors in fibroblasts. This reduction is an intracellular effect, not caused by TGF-alpha, and EGF receptors are not essential for src-induced cell transformation.
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- The src oncogene plays a role in cell transformation and growth regulation.
- Epidermal Growth Factor (EGF) receptors are critical for cell signaling and proliferation.
Purpose of the Study:
- To investigate the impact of src oncogene expression on EGF receptor levels in fibroblasts.
- To determine the mechanism behind EGF receptor downregulation in src-transformed cells.
- To assess the necessity of EGF receptors for src-mediated cell transformation.
Main Methods:
- Fibroblast cell lines (mouse 3T3 and rat-1) were transformed with the src oncogene.
- EGF receptor levels were quantified using 125I-EGF binding assays and immunoprecipitation.
- Culture supernatants were analyzed for transforming growth factor-alpha (TGF-alpha).
- An EGF-receptorless cell line was infected with src to evaluate transformation criteria.
Main Results:
- Src oncogene expression led to significant reductions in cellular EGF receptor levels.
- The downregulation of EGF receptors was not attributed to secreted TGF-alpha.
- Src-transformed cells lacking EGF receptors still exhibited characteristics of transformation.
- These findings suggest an intracellular mechanism for EGF receptor modulation by pp60src.
Conclusions:
- pp60src downregulates EGF receptors through an intracellular mechanism.
- The loss of EGF receptors is a consequence of broader effects of pp60src on growth regulation machinery.
- EGF receptors are not essential for the src oncogene's transformation process.