Platelet-derived growth factor (PDGF) B and A homodimers transform murine fibroblasts depending on the genetic background of the cell.
The endogenously overexpressed c-sis (platelet-derived growth factor (PDGF) B-chain) proto-oncogene and its viral counterpart v-sis effectively transform NIH 3T3 cells by an autocrine mechanism, whereas the PDGF A-chain gene does not. However, PDGF B continuously cultured with confluent NIH 3T3 cells fails to induce phenotypic transformation as would be predicted by the autocrine model. We now have established conditions in which subconfluent, logarithmically growing NIH 3T3 cells are efficiently transformed by exogenous PDGF B but not PDGF A. Clonally selected cells from transformed foci remain transformed when continuously cultured with PDGF B but revert to the non-transformed phenotype without PDGF B or if PDGF A is substituted for PDGF B, suggesting that PDGF B complements a genetically stable NIH 3T3 cell phenotype to induce transformation and initiates a signal different from that of PDGF A required to induce transformation. Neither PDGF A nor PDGF B transform normal rat kidney (NRK) cells under identical conditions of culture. However, we now demonstrate that exogenous PDGF A and PDGF B independently transform NRK cells that endogenously overexpress the anti-apoptotic bcl-2 gene. These results suggest that both PDGF A and PDGF B effectively transform murine fibroblasts with a compatible genotype, that transformation by the PDGF isoforms requires complementation with a compatible genotype in a multistep transformational process, and that the autocrine mechanism is required but not sufficient for transformation of murine fibroblasts by PDGF.
Kim
H R
HR
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Upadhyay
S
S
Korsmeyer
S
S
Deuel
T F
TF
D016475:3T3 Cells; D000818:Animals; D000077214:Becaplermin; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D005347:Fibroblasts / Q000187:drug effects; D007668:Kidney; D051379:Mice; D020575:Oncogene Proteins v-sis; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2; D020574:Proto-Oncogene Proteins c-sis; D011519:Proto-Oncogenes; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics; D013045:Species Specificity; D014162:Transfection
D020575:Oncogene Proteins v-sis; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D015682:Retroviridae Proteins, Oncogenic; C075278:platelet-derived growth factor A; D000077214:Becaplermin; D011505:Protein-Tyrosine Kinases