The oncogene PDGF-B provides a key switch from cell death to survival induced by TNF

Tumor necrosis factor (TNF) induces both cell death and survival signals. NF-kappa B, a transcription factor activated by TNF, is critical for controlling survival signals through trans-activation of downstream target genes. However, few NF-kappa B target survival genes have been identified with direct roles in oncogenesis. We report that platelet-derived growth factor B (PDGF-B), an oncogene and growth factor, is highly induced by TNF in fibroblasts in an NF-kappa B-dependent manner. PDGF-B can rescue NF-kappa B deficient. broblasts from TNF-mediated killing, and inhibition of PDGF-B signaling sensitizes wild-type cells to TNF-induced death. Interestingly, PDGF-B-transformed NIH-3T3 cells are even more highly sensitized to TNF-induced cell death with PDGF-B inhibition. Our results suggest that while normal cells contain multiple TNF-induced survival signals, tumor cells may favor a specific survival gene that is abnormally upregulated in order to evade death signals.