INTERLEUKIN-1 INCREASES EXPRESSION OF THE LYT-10 (NF-KAPPA-B2) PROTOONCOGENE TRANSCRIPTION FACTOR IN RENAL-CELL CARCINOMA LINES

The LYT-10 gene was initially cloned by virtue of its disruption by th e translocation breakpoint in some t(10;14) lymphoid neoplasms, LYT-10 is now known to encode a component of the NF-kappa B family of transc riptional activators and has therefore also been designated NF kappa B 2. Activation of NF-kappa B is generally associated with its transfer to the nucleus and is followed by a rapid increase in expression of it s target genes, which include cytokines such as interleukin-6 (IL-6), 11-6 can also be induced by other transcription factors such as NF-IL6 , We studied the interaction of IL-1 and these transcription factors i n two renal cell carcinoma cell lines (ACHN and Caki-1). These lines p roduce high levels of IL-6, show endogenous chloramphenicol acetyltran sferase activity for the 11-6 promoter, and have high basal levels of transcripts encoding the NF-kappa B components Lyt-10, p50, and p65 as well as the NF-IL6 transcription factor, IL-1 alpha and IL-1 beta mar kedly increased steady-state levels of LYT-10 (NF kappa B2) transcript s and nuclear Lyt-10 protein in both cell lines. Levels of the NF kapp a B1 (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 11-6 messenger ribonucleic acid (mRNA) and prote in. Our observations suggest that the mechanism by which IL-1 alpha or IL-1 beta induces IL-6 may be mediated through increases in LYT-10 mR NA and protein levels as well as increases in expression of other tran scription factors (NF kappa B1, p65, and NF-IL6), in addition to the k nown ability of IL-1 to post-translationally activate NF-kappa B.