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SV40 virus transformation down-regulates endothelin receptor
1Pharmaceutical Products Division, D-47H, AP9A, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA.
Biochimica Et Biophysica Acta
|May 8, 1999
Summary
Simian virus 40 (SV40) transformation down-regulates endothelin (ET) receptors in human lung fibroblasts. ET receptor expression is inversely correlated with SV40 large T-antigen levels, impacting cell proliferation.
Area of Science:
- Oncology
- Molecular Biology
- Virology
Background:
- Simian virus 40 (SV40) is an oncogenic DNA virus known to induce malignant transformation.
- Endothelin (ET) is a peptide hormone with mitogenic and anti-apoptotic properties, acting via ETA and ETB receptors.
Purpose of the Study:
- To investigate the impact of SV40 transformation on the expression of endothelin (ET) receptors.
- To determine the correlation between SV40 large T-antigen expression and ET receptor levels.
Main Methods:
- Receptor binding assays were performed to quantify ET receptor levels.
- Reverse transcription (RT)-polymerase chain reaction (PCR) was used to assess ET receptor gene expression.
- SV40-transformed cell lines (IMR90-SV40, WI38-SV40) and a temperature-sensitive SV40 large T-antigen expressing cell line (3A(tPA-30-1)) were utilized.
Main Results:
- Human lung fibroblasts (IMR90, WI38) express both ETA and ETB receptors.
- SV40 transformation significantly down-regulated ETA and ETB receptor expression in IMR90 and WI38 cells.
- An inverse correlation was observed between SV40 large T-antigen expression and ET receptor levels.
Conclusions:
- SV40 transformation leads to a significant decrease in endothelin receptor expression.
- The expression of ET receptors is inversely related to the expression of SV40 large T-antigen.
- Cell proliferation in SV40-transformed cells becomes independent of ET-1 and serum growth factors.