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Negative trans-acting mechanisms controlling expression of platelet-derived growth factor A and B MRNA in somatic
P Levéen1, C Betsholtz, B Westermark
1Department of Pathology, University Hospital, Uppsala, Sweden.
Abstract:
We have studied a human malignant melanoma cell line (WM115) which expresses high levels of PDGFA and PDGFB mRNAs, a hamster fibroblast cell line (Wq3H) which lacks PDGFB and has a very low expression of PDGFA mRNA, and hybrids between these cell lines. The PDGFA and PDGFB mRNA expression in the hybrid cells was markedly suppressed, indicating that the melanoma PDGF genes are controlled in the hybrid cells by negative factors/mechanisms contributed by the fibroblast genome. The melanoma but not the fibroblast PDGFB mRNA was induced by cycloheximide in the hybrid cells, indicating that the fibroblast and the melanoma PDGFB genes are regulated differently despite their presence in the same intracellular environment.
Insights
Melanoma cells show suppressed PDGF gene expression when hybridized with fibroblasts, suggesting fibroblast genes regulate melanoma growth factors. Different regulation of PDGFB mRNA in hybrids highlights distinct gene control mechanisms.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Human malignant melanoma cell lines (WM115) exhibit high expression of Platelet-Derived Growth Factor A (PDGFA) and Platelet-Derived Growth Factor B (PDGFB) mRNAs.
- Hamster fibroblast cell lines (Wq3H) show very low PDGFA mRNA expression and lack PDGFB mRNA.
- Understanding the regulation of PDGF genes is crucial in melanoma research.
Purpose of the Study:
- To investigate the regulation of PDGFA and PDGFB gene expression in melanoma cells.
- To determine the role of fibroblast-derived factors in controlling melanoma PDGF gene expression.
- To compare the regulation of PDGFB mRNA in melanoma and fibroblast cells within a hybrid environment.
Main Methods:
- Generation of hybrid cell lines by fusing human melanoma cells (WM115) and hamster fibroblast cells (Wq3H).
- Analysis of PDGFA and PDGFB mRNA expression levels in parental and hybrid cell lines.
- Induction of PDGFB mRNA expression using cycloheximide in hybrid cells.
Main Results:
- PDGFA and PDGFB mRNA expression was significantly suppressed in hybrid cells compared to the melanoma parent cells.
- Melanoma-derived PDGFB mRNA, but not fibroblast-derived PDGFB mRNA, was inducible by cycloheximide in hybrid cells.
- These findings suggest the presence of negative regulatory factors from the fibroblast genome controlling melanoma PDGF genes.
Conclusions:
- Fibroblast genomes contain negative regulatory factors that suppress melanoma PDGF gene expression.
- Melanoma and fibroblast PDGFB genes are differentially regulated, even within the same cellular context of a hybrid cell.
- This differential regulation provides insights into the complex mechanisms governing growth factor expression in cancer cells.