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

Oncogene volume 24, pages 3196–3205 (2005)Cite this article

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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Authors and Affiliations

  1. AMDI/cFIFBCR, University Health Network, Department of Medical Biophysics, University of Toronto, 620 University Ave. Suite 7-706, Toronto, Ontario, Canada, M5G 2C1

    P Y Billie Au, Nicole Martin, Hien Chau, Behrouz Moemeni & Wen-Chen Yeh

  2. Ontario Cancer Institute, University Health Network, 610 University Ave, Toronto, Ontario, Canada, M5G 2M9

    Marie Chia, Fei-Fei Liu & Mark Minden

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  1. P Y Billie Au
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Correspondence to Wen-Chen Yeh.

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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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