title: The oncogene PDGF-B provides a key switch from cell death to survival induced by TNF.
abstract: Tumor necrosis factor (TNF) induces both cell death and survival signals. NF-kappaB, a transcription factor activated by TNF, is critical for controlling survival signals through trans-activation of downstream target genes. However, few NF-kappaB 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-kappaB-dependent manner. PDGF-B can rescue NF-kappaB-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.
authors.affiliation: AMDI/cFIFBCR, University Health Network, Department of Medical Biophysics, University of Toronto, 620 University Ave. Suite 7-706, Toronto, Ontario, Canada M5G 2C1.
authors.forename: P Y Billie
authors.initials: PY
authors.lastname: Au
authors.forename: Nicole
authors.initials: N
authors.lastname: Martin
authors.forename: Hien
authors.initials: H
authors.lastname: Chau
authors.forename: Behrouz
authors.initials: B
authors.lastname: Moemeni
authors.forename: Marie
authors.initials: M
authors.lastname: Chia
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Liu
authors.forename: Mark
authors.initials: M
authors.lastname: Minden
authors.forename: Wen-Chen
authors.initials: WC
authors.lastname: Yeh
mesh_terms: D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D015152:Blotting, Northern; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D002461:Cell Line, Transformed; D002469:Cell Separation; D002470:Cell Survival; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D051550:I-kappa B Kinase; D051379:Mice; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D041681:NIH 3T3 Cells; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D016895:Culture Media, Serum-Free; D016328:NF-kappa B; D020574:Proto-Oncogene Proteins c-sis; D014409:Tumor Necrosis Factor-alpha; D017479:Receptors, Platelet-Derived Growth Factor; D017346:Protein Serine-Threonine Kinases; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases