Abstract
Tumor necrosis factor (TNF) induces both cell death and survival signals. NF-κB, a transcription factor activated by TNF, is critical for controlling survival signals through trans-activation of downstream target genes. However, few NF-κB 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-κB-dependent manner. PDGF-B can rescue NF-κB-deficient fibroblasts 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.
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Acknowledgements
We thank Carl-Henrik Heldin, Arne Östman, Stuart Aaronson, Bruce Horwitz, and Tak W Mak for reagents and helpful advice. We thank Jim Woodgett and Wen-Jye Lin for valuable discussion; Nien-Jung Chen, Huey-Lan Huang, Christine Mirtsos, and Denis Bouchard for technical assistance; and Linh Nguyen for her help in editing the manuscript. PYBAu is funded by the Canadian Institute of Health Research (MD/PhD Studentship). This research was supported by the National Cancer Institute of Canada with funds from the Canadian Cancer Society (NCIC 13150).
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Billie Au, P., Martin, N., Chau, H. et al. The oncogene PDGF-B provides a key switch from cell death to survival induced by TNF. Oncogene 24, 3196–3205 (2005). https://doi.org/10.1038/sj.onc.1208516
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DOI: https://doi.org/10.1038/sj.onc.1208516
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