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Imbalanced expression of cellular nuclear oncogenes caused by v-sis/PDGF-2
M H Sonobe1, R Bravo, M S Armelin
1Departamento de Bioquímica, Universidade de São Paulo, Brazil.
Oncogene
|September 1, 1991
Summary
Simian sarcoma virus (SSV) infection causes cell transformation by overexpressing v-sis/PDGF-2. This leads to deregulated gene expression, uncontrolled cell growth, and malignancy in murine cells.
Area of Science:
- Molecular Biology
- Oncology
- Virology
Background:
- Murine cell lines overexpressing v-sis/PDGF-2 were utilized to investigate simian sarcoma virus (SSV) induced cell transformation.
- Parental cells exhibit normal phenotype and serum-dependent growth, while v-sis-overexpressing cells display altered growth and tumorigenic properties.
Purpose of the Study:
- To elucidate the mechanism of cell transformation mediated by SSV.
- To analyze the expression patterns of growth factor-induced early response genes in v-sis-overexpressing cells.
Main Methods:
- Overexpression of v-sis/PDGF-2 in murine cell lines.
- Analysis of phenotypic changes including growth characteristics and tumorigenicity.
- Quantitative assessment of specific gene and protein expression levels (e.g., c-myc, FOS, JUN).
Main Results:
- v-sis-overexpressing cells exhibit PDGF-independent growth, resistance to G0 arrest, and high tumorigenicity.
- Constitutive expression of c-myc mRNA and FOS proteins observed.
- Unaltered levels of fra-1, fos B, jun B, and krox 20, but constitutive c-JUN and increased JUN D expression.
Conclusions:
- Endogenous v-sis/PDGF-2 production drives deregulated expression of cellular transregulators.
- Altered transcriptional programs in v-sis-overexpressing cells lead to transformation and malignancy.
- Findings support a model linking PDGF-2 signaling to oncogenesis via transcriptional dysregulation.