Interleukin-6 signal communication to the alpha 1-acid glycoprotein gene, but not junB gene, is impaired in HTC cells.
In the rat hepatoma (HTC) cell line, transcription of the alpha 1-acid glycoprotein (AGP) gene is prominently stimulated by dexamethasone. Although interleukin (IL)-1 and IL-6 synergistically enhance expression of the AGP gene in liver, they have no detectable effect on this gene in HTC cells. Nevertheless, HTC cells have mRNA encoding the IL-6 receptor subunits and respond to IL-6 by increasing expression of the junB gene. The mRNA for the 80-kDa IL-6 receptors is increased severalfold following dexamethasone treatment. Even with elevated IL-6 receptor expression, no IL-6 regulation of the AGP gene is observed. The lack of response to IL-6 is also found with the transfected AGP gene sequence, suggesting the absence of specific trans-acting factors. Since IL-6 promotes only a minimal stimulation of the CCAAT/enhancer-binding protein beta, HTC cells lack the indirect IL-6 signaling pathway to acute phase plasma protein genes that has been found to be crucial in other hepatoma cell lines. Considering that a similar IL-6 regulation of the junB gene is manifested in HTC cells and normal liver, a separate IL-6 signal-transducing pathway controlling the AGP gene is assumed to be missing in HTC cells.
Baumann
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Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York 14263.
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D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016758:Genes, jun / Q000187:drug effects*; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology*; D008114:Liver Neoplasms, Experimental; D009961:Orosomucoid / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D019947:Receptors, Interleukin-6; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D009961:Orosomucoid; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D014157:Transcription Factors; D003907:Dexamethasone