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.
journal_name
Oncogenejournal_title
Oncogeneauthors
Au PY,Martin N,Chau H,Moemeni B,Chia M,Liu FF,Minden M,Yeh WCdoi
10.1038/sj.onc.1208516subject
Has Abstractpub_date
2005-04-28 00:00:00pages
3196-205issue
19eissn
0950-9232issn
1476-5594pii
1208516journal_volume
24pub_type
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