Differential effects of PDGF isoforms on proliferation of normal rat kidney cells
| Autor: | Van de Wetering Ra, Van Rotterdam W, Carl-Henrik Heldin, van Zoelen Ej |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Gene isoform
Cell division Clinical Biochemistry Down-Regulation Kidney Cell Line Endocrinology Epidermal growth factor Animals Humans Receptors Platelet-Derived Growth Factor Receptor Platelet-Derived Growth Factor biology Epidermal Growth Factor Biological activity Cell Biology Cell biology Rats Biochemistry Cell culture biology.protein Anchorage-Independent Growth Platelet-derived growth factor receptor Cell Division |
| Zdroj: | Growth Factors, 9, 329-339 Growth Factors, 9, 4, pp. 329-339 |
| ISSN: | 0897-7194 |
| Popis: | The effects of the PDGF isoforms AA, AB and BB have been studied on the proliferation of normal rat kidney cells, a non-tumorigenic fibroblast cell line which contains both type alpha and type beta PDGF receptors. On monolayer cells made quiescent by serum deprivation, PDGF-AA is a relatively poor mitogen compared to PDGF-AB and PDGF-BB. When these cells are made density-arrested following continuous incubation with epidermal growth factor, however, they can be restimulated to proliferate by all three PDGF isoforms with similar activity when added at sufficiently high concentration, resulting in phenotypic cellular transformation. Binding of radiolabelled isoforms to confluent NRK monolayers obeys the predictions of an induced receptor dimerisation model, and increases in the order AA < AB < BB. Upon preincubation of the cells with PDGF-AA, the dose-response curve for mitogenic activity of PDGF-AB is shifted to higher concentrations, indicating that PDGF-AA can partly antagonize the growth stimulating activity of PDGF-AB, as has also been observed in ligand binding studies. This observation has subsequently been confirmed using fluorescence cytometric analysis. PDGF-AB is highly active in inducing anchorage-independent proliferation of NRK cells, but in all such assays PDGF-AA is at least as potent as PDGF-BB. Intriguingly, PDGF-BB is almost devoid of activity in inducing soft agar growth of these cells, in contrast to PDGF-AA. When compared to substrate-attached cells, enhanced expression of the type alpha PDGF receptor was observed under anchorage-independent conditions. These results show that the relative potency of the three PDGF isoforms to stimulate proliferation of NRK cells is different for quiescent cells in monolayer, density-arrested cells and anchorage-independent cells. Moreover it is shown that the biological activity of PDGFs can be impaired by the additional presence of other isoforms. |
| Databáze: | OpenAIRE |
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