Activation of NF-κB Is Required for PDGF-B Chain to Transform NIH3T3 Cells

Abstract

Elucidating the secondary signaling molecules that are necessary for platelet-derived growth factor (PDGF) to stimulate tumor development will be crucial to the understanding and treatment of a variety of cancers. Several lines of evidence have indicated that the transcription factor NF-κB plays a central role in transformation induced by Ha-ras and Bcr-abl, but nothing is known concerning its role in transformation by PDGF. Here we demonstrate that transcription from a promoter containing NF-κB binding sequences as well as the DNA binding activity of NF-κB were increased in PDGF-B-chain-transformed mouse fibroblast cells. Focus formation of PDGF-B-chain-transformed mouse fibroblasts was suppressed by treatment with acetylsalicylic acid (ASA) and salicylic acid, which are known inhibitors of NF-κB activation, but other nonsteroidal anti-inflammatory drugs that do not have an effect on NF-κB activity did not affect focus formation in these cells. Furthermore, expression of a dominant negative mutant of IκBα, pMEIκBα67CJ, and a dominant negative mutant of p65, p65ΔC, resulted in decreased focus formation and NF-κB activity. Therefore, the transcription factor NF-κB plays a vital role in PDGF-B chain transformation of mouse fibroblast cells, and the NF-κB activity is sensitive to treatment with ASA.