In earlier studies we showed that the expression of patterns of
platelet-derived growth factor (PDGF) alpha- and beta-receptors differ between normal and malignant mesothelial cell lines. Normal mesothelial cells predominantly express
PDGF alpha-receptor mRNA and
protein, whereas most
malignant mesothelioma cell lines produce
PDGF beta-receptor mRNA and
protein. In this paper we studied regulation of this differential
PDGF receptor mRNA expression. Such an analysis is of importance in view of the suggested PDGF autocrine activity involving the
PDGF beta-receptor mesothelioma cells. The results obtained in this study demonstrate that
malignant mesothelioma cell lines are not only capable of
PDGF beta-receptor transcription but of alpha-receptor transcription as well, as evidenced from run off analysis and RT-PCR using alpha-receptor specific primers. However, the fact that
PDGF alpha-receptor mRNA could not be detected by Northern blot analysis, even after
cycloheximide treatment, suggests a difference in steady-state
PDGF alpha-receptor mRNA expression levels between normal and malignant mesothelial cell lines, which is likely to be caused by a post-transcriptional mechanism. In normal mesothelial cells a half-life of more than 6 h was observed for
PDGF alpha-receptor mRNA. In the majority of
malignant mesothelioma cell lines clear
PDGF beta-receptor mRNA expression was seen. The half-life of the
PDGF beta-receptor transcript was at least 6 h in these cells. In contrast, hardly any
PDGF beta-receptor transcription was observed in run off assays in normal mesothelial cells, suggesting that differences in beta-receptor transcriptional initiation most probably account for the inability to clearly detect
PDGF beta-receptor transcripts in these cells.
Transforming growth factor beta-1 (TGF-beta 1), which is being produced in active form by mesothelial cells was evaluated for its potential role in regulation of the differential
PDGF receptor expression in these cells. Stimulation with
TGF-beta 1 revealed decreased
PDGF alpha-receptor mRNA expression in normal mesothelial cells. The effect on
PDGF beta-receptor mRNA in the
malignant mesothelioma cell lines was variable. Although the
TGF-beta 1 effect cannot entirely explain the differential
PDGF receptor expression pattern,
TGF-beta 1 may nevertheless play a role in downregulation of an (already) low
PDGF alpha-receptor mRNA level in
malignant mesothelioma cell lines.