Failure of the splicing variant p65 delta of the NF-kappa B subunit p65 to transform fibroblasts.

A naturally occurring splice variant of the p65 subunit of the inducible transcription factor NK-kappa B, called p65 delta, has recently been reported to transform rat-1 fibroblasts in transfection experiments. Criteria for transformation included focus formation, growth in soft agar and tumor formation in athymic mice. In the present study we provide evidence that p65 delta cannot transform either rat-1 or rat-2 cells although p65 delta was efficiently expressed and showed all transcriptional activities reported previously. Eleven rat-1 fibroblasts cells lines selected for stably overexpressing p65 delta also showed neither focus formation nor anchorage-independent growth in soft agar. No transformation of primary rat fibroblasts was evident when p65 delta was cotransfected with either ras or myc oncogenes, whereas a combination of the two oncogenes caused focus formation. We submit that the transforming potential of p65 delta is highly conditional and presumably restricted to a particular subclone of rat-1 cells.