Immortalized embryonic mouse fibroblasts lacking the RelA subunit of transcription factor NF-kappaB have a malignantly transformed phenotype.
The RelA transcription factor is part of dimeric complexes, most commonly either p50-RelA (NF-kappaB) heterodimers or RelA homodimers, that control a variety of cellular processes. Immortalized embryonic fibroblasts established from rela knockout mice have previously been shown to be more sensitive to apoptosis induced by tumor necrosis factor (TNF) than are control fibroblasts. In this report, we show that one line of rela-/- fibroblasts has additional phenotypes that distinguish them from control mouse fibroblasts. As compared to normal 3T3 cells, RelA-deficient fibroblasts have a spindled morphology, are less adherent to culture dishes, grow to a higher saturation density, and can form colonies in soft agar. These properties are consistent with a weakly transformed phenotype for rela-/- cells. Furthermore, RelA-deficient fibroblasts can form tumors in immunodeficient mice, but these tumors regress, probably because of the sensitivity of these cells to TNF. The ability of rela-/- fibroblasts to form colonies in soft agar can be reverted by re-expression of wild-type mouse RelA, but not by expression of RelA mutants that cannot form homodimers. There is no clear correlation between the absence of RelA and the levels of expression of other Rel/NF-kappaB family members or adhesion proteins (ICAM-1 and VCAM-1) whose genes have upstream kappaB sites. Taken together, these results suggest that RelA has tumor suppressing activity under some circumstances and that RelA complexes are involved in the control of a variety of cellular properties associated with oncogenesis.
Gapuzan
Maria-Emily R
ME
Biology Department, Boston University, 5 Cummington Street, Boston, MA 02215, USA.
Yufit
Pavel V
PV
Gilmore
Thomas D
TD
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion; D002455:Cell Division; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D019281:Dimerization; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D009154:Mutation; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology*; D009374:Neoplasms, Experimental / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D051996:Transcription Factor RelA; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014410:Tumor Stem Cell Assay
D016328:NF-kappa B; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha