Interleukin-1 increases expression of the LYT-10 (NFκB2) proto-oncogene/transcription factor in renal cell carcinoma lines

The LYT-10 gene was initially cloned by virtue of its disruption by translocation breakpoint in some t(10;14) lymphoid neoplasms. LYT-10 is now known to encode a component of the NF-κB family of transcriptional activators and has therefore also been designed NFκB2. Activation of NF-κB is generally associated with its transfer to the nucleus and is followed by a rapid increase in expression of its target genes, which include cytokines such as interleukin-6 (IL-6). IL-6 can also be induced by other transcription factors such as NF-IL6. We studied the interaction of IL-1 and these transcription factors in two renal cell carcinoma cell lines (ACHN and Caki-1). These lines produce high levels of IL-6, show endogenous chloramphenicol acetyl-transferase activity for the IL-6 promoter, and have high basal levels of transcripts encoding the NF-κB components Lyt-10, p50, and p65 as well as the NF-IL6 trancription factor. IL-1α and IL-1β markedly increased steady-state levels of LYT-10 (NFκB2) transcripts and nuclear Lyt-10 protein in both cell lines. Levels of the NFκB1 (p50-encoding), p65, and NF-IL6 transcripts also increased after IL-1 exposure. These changes were accompanied by a 20-fold or greater increase in levels of IL-6 messenger ribonucleic acid (mRNA) and protein. Our observations suggest that the mechanism by which IL-1α or IL-1β induces IL-6 may be mediated through increases in LYT-10 mRNA and protein levels as well as increases in expression of other transcription factors (NFκB1, p65, and NF-IL6), in addition to the known ability of IL-1 to post-translationally activate NF-κB.