Interleukin-1 increases expression of the LYT-10 (NFkappaB2) proto-oncogene/transcription factor in renal cell carcinoma lines.
The LYT-10 gene was initially cloned by virtue of its disruption by the translocation breakpoint in some t(10;14) lymphoid neoplasms. LYT-10 is now known to encode a component of the NF-kappaB family of transcriptional activators and has therefore also been designated NFkappaB2. Activation of NF-kappaB 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 acetyltransferase activity for the IL-6 promoter, and have high basal levels of transcripts encoding the NF-kappaB components Lyt-10, p50, and p65 as well as the NF-IL6 transcription factor. IL-1alpha and IL-1beta markedly increased steady-state levels of LYT-10 (NFkappaB2) transcripts and nuclear Lyt-10 protein in both cell lines. Levels of the NFkappaB1 (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-1alpha or IL-1beta 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 (NFkappaB1, p65, and NF-IL6), in addition to the known ability of IL-1 to post-translationally activate NF-kappaB.
Kurzrock
R
R
Department of Bioimmunotherapy, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Estrov
Z
Z
Ku
S
S
Leonard
M
M
Talpaz
M
M
D015152:Blotting, Northern; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D052003:NF-kappa B p52 Subunit; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007375:Interleukin-1; D015850:Interleukin-6; C000715470:MAS1 protein, human; D016328:NF-kappa B; D052003:NF-kappa B p52 Subunit; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015500:Chloramphenicol O-Acetyltransferase