Activation of NF-kappaB is required for PDGF-B chain to transform NIH3T3 cells.
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-kappaB 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-kappaB binding sequences as well as the DNA binding activity of NF-kappaB 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-kappaB activation, but other nonsteroidal anti-inflammatory drugs that do not have an effect on NF-kappaB activity did not affect focus formation in these cells. Furthermore, expression of a dominant negative mutant of IkappaBalpha, pMEIkappaBalpha67CJ, and a dominant negative mutant of p65, p65DeltaC, resulted in decreased focus formation and NF-kappaB activity. Therefore, the transcription factor NF-kappaB plays a vital role in PDGF-B chain transformation of mouse fibroblast cells, and the NF-kappaB activity is sensitive to treatment with ASA.
Shimamura
Takeshi
T
Department of Biological Sciences, Western Michigan University, Kalamazoo, Michigan 49008, USA.
Hsu
Tin-Chen
TC
Colburn
Nancy H
NH
Bejcek
Bruce E
BE
D016475:3T3 Cells; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced; D020672:I-kappa B Proteins / Q000235:genetics / Q000494:pharmacology; D051379:Mice; D009154:Mutation; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D020574:Proto-Oncogene Proteins c-sis / Q000502:physiology*; D015290:Second Messenger Systems
D020672:I-kappa B Proteins; D016328:NF-kappa B; D020574:Proto-Oncogene Proteins c-sis; D001241:Aspirin