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P21 v-ras inhibits induction of c-myc and c-fos expression by platelet-derived growth factor
1Division of Pediatric Hematology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Abstract:
The viral oncogene v-ras inhibited the platelet-derived growth factor (PDGF)-induced upregulation of c-myc and c-fos proto-oncogene expression in fibroblast monolayers. These v-ras-containing cells proliferated in the absence of c-myc induction and no longer required PDGF to support growth. Fibroblasts expressing v-ras continued to express the same number of functional PDGF receptors on their surface as uninfected cells, yet the usual induction of transcription of the genes c-myc, c-fos, and JE in response to PDGF stimulation did not occur in the presence of newly introduced v-ras or chronic v-ras gene expression, and synthesis of c-myc protein did not occur. This inhibitory effect on growth factor-mediated induction of cellular proto-oncogenes was specific for PDGF in that induction of the c-myc and c-fos genes by certain other factors was not impaired.
Insights
The viral oncogene v-ras blocks platelet-derived growth factor (PDGF) from activating key genes like c-myc and c-fos. This allows cells with v-ras to grow without PDGF signals.
Area of Science:
- Molecular Biology
- Oncology
- Cell Biology
Background:
- Platelet-derived growth factor (PDGF) is crucial for cell growth and regulates proto-oncogene expression.
- Viral oncogenes, such as v-ras, can disrupt normal cellular processes and contribute to uncontrolled proliferation.
Purpose of the Study:
- To investigate the effect of the viral oncogene v-ras on PDGF-induced proto-oncogene expression in fibroblasts.
- To determine if v-ras interferes with the signaling pathway initiated by PDGF.
Main Methods:
- Fibroblast monolayers were infected with v-ras.
- Cells were stimulated with PDGF, and the expression of c-myc, c-fos, and JE proto-oncogenes was analyzed.
- PDGF receptor expression and function were assessed in v-ras-expressing cells.
Main Results:
- v-ras expression inhibited PDGF-induced upregulation of c-myc and c-fos proto-oncogenes.
- Fibroblasts expressing v-ras proliferated independently of PDGF and c-myc induction.
- v-ras did not affect the number of functional PDGF receptors but blocked downstream signaling.
- The inhibitory effect was specific to PDGF, as other growth factors could still induce c-myc and c-fos.
Conclusions:
- The viral oncogene v-ras interferes with PDGF-mediated signal transduction, specifically inhibiting the induction of key proto-oncogenes.
- This disruption leads to growth factor-independent proliferation, a hallmark of oncogenic transformation.
- v-ras provides a model for understanding how viral oncogenes can override normal cellular growth control mechanisms.