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.

journal_name

Oncogene

journal_title

Oncogene

authors

Au PY,Martin N,Chau H,Moemeni B,Chia M,Liu FF,Minden M,Yeh WC

doi

10.1038/sj.onc.1208516

subject

Has Abstract

pub_date

2005-04-28 00:00:00

pages

3196-205

issue

19

eissn

0950-9232

issn

1476-5594

pii

1208516

journal_volume

24

pub_type

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