1887

Abstract

Cervical carcinoma cells producing high levels of interleukin-6 (IL-6) were shown to be unresponsive to the cytokine IL-6 due to the loss of their IL-6 receptor. Addition of IL-6 receptor in a soluble form restores IL-6 signalling in SW756 carcinoma cells. This leads to a rapid and strong activation of the transcription factor signal transducer and activator of transcription 3 (STAT3). Nuclear factor IL-6 (NF-IL6, C/EBPβ) was induced only as a late event. While C/EBPβ significantly repressed the human papillomavirus type 18 long control region (HPV18-LCR), IL-6 signalling unexpectedly activated the HPV18-LCR in these cells. This IL-6 receptor-mediated induction could be completely reverted by transfection of a dominant-negative STAT3 but not STAT1 expression construct, indicating that STAT3 might play an important role in HPV18 oncogene promoter activation.

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2001-10-01
2019-10-22
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References

  1. Akira, S., Isshiki, H., Sugita, T., Tanabe, O., Kinoshita, S., Nishio, Y., Nakajima, T., Hirano, T. & Kishimoto, T. ( 1990; ). A nuclear factor for IL-6 expression (NF-IL6) is a member of a C/EBP family. EMBO Journal 9, 1897-1906.
    [Google Scholar]
  2. Altenburg, A., Baldus, S. E., Smola, H., Pfister, H. & Hess, S. ( 1999; ). CD40 ligand–CD40 interaction induces chemokines in cervical carcinoma cells in synergism with IFN-gamma. Journal of Immunology 162, 4140-4147.
    [Google Scholar]
  3. Bauknecht, T., See, R. H. & Shi, Y. ( 1996; ). A novel C/EBP beta–YY1 complex controls the cell-type-specific activity of the human papillomavirus type 18 upstream regulatory region. Journal of Virology 70, 7695-7705.
    [Google Scholar]
  4. Bauknecht, T., Randelzhofer, B., Schmitt, B., Ban, Z., Hernando, J. J. & Bauknecht, T. ( 1999; ). Response to IL-6 of HPV-18 cervical carcinoma cell lines. Virology 258, 344-354.[CrossRef]
    [Google Scholar]
  5. Baumann, H., Morella, K. K., Campos, S. P., Cao, Z. & Jahreis, G. P. ( 1992; ). Role of CAAT-enhancer binding protein isoforms in the cytokine regulation of acute-phase plasma protein genes. Journal of Biological Chemistry 267, 19744-19751.
    [Google Scholar]
  6. Boulton, T. G., Stahl, N. & Yancopoulos, G. D. ( 1994; ). Ciliary neurotrophic factor/leukemia inhibitory factor/interleukin 6/oncostatin M family of cytokines induces tyrosine phosphorylation of a common set of proteins overlapping those induced by other cytokines and growth factors. Journal of Biological Chemistry 269, 11648-11655.
    [Google Scholar]
  7. Chen, L., Mory, Y., Zilberstein, A. & Revel, M. ( 1988; ). Growth inhibition of human breast carcinoma and leukemia/lymphoma cell lines by recombinant interferon-beta 2. Proceedings of the National Academy of Sciences, USA 85, 8037-8041.[CrossRef]
    [Google Scholar]
  8. Daeipour, M., Kumar, G., Amaral, M. C. & Nel, A. E. ( 1993; ). Recombinant IL-6 activates p42 and p44 mitogen-activated protein kinases in the IL-6 responsive B cell line, AF-10. Journal of Immunology 150, 4743-4753.
    [Google Scholar]
  9. Eustace, D., Han, X., Gooding, R., Rowbottom, A., Riches, P. & Heyderman, E. ( 1993; ). Interleukin-6 (IL-6) functions as an autocrine growth factor in cervical carcinomas in vitro. Gynecologic Oncology 50, 15-19.[CrossRef]
    [Google Scholar]
  10. Heinrich, P. C., Behrmann, I., Muller-Newen, G., Schaper, F. & Graeve, L. ( 1998; ). Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochemistry Journal 334, 297-314.
    [Google Scholar]
  11. Hess, S., Smola, H., Sandaradura De Silva, U., Hadaschik, D., Kube, D., Baldus, S. E., Flucke, U. & Pfister, H. ( 2000; ). Loss of IL-6 receptor expression in cervical carcinoma cells inhibits autocrine IL-6 stimulation: abrogation of constitutive monocyte chemoattractant protein-1 production. Journal of Immunology 165, 1939-1948.[CrossRef]
    [Google Scholar]
  12. Hibi, M., Murakami, M., Saito, M., Hirano, T., Taga, T. & Kishimoto, T. ( 1990; ). Molecular cloning and expression of an IL-6 signal transducer, gp130. Cell 63, 1149-1157.[CrossRef]
    [Google Scholar]
  13. Hirano, T., Nakajima, K. & Hibi, M. ( 1997; ). Signaling mechanisms through gp130: a model of the cytokine system. Cytokine & Growth Factor Reviews 8, 241-252.[CrossRef]
    [Google Scholar]
  14. Hirano, T., Ishihara, K. & Hibi, M. ( 2000; ). Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors. Oncogene 19, 2548-2556.[CrossRef]
    [Google Scholar]
  15. Kawano, M., Hirano, T., Matsuda, T., Taga, T., Horii, Y., Iwato, K., Asaoku, H., Tang, B., Tanabe, O., Tanaka, H. and others ( 1988; ). Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas. Nature 332, 83–85.[CrossRef]
    [Google Scholar]
  16. Klein, B., Zhang, X. G., Lu, Z. Y. & Bataille, R. ( 1995; ). Interleukin-6 in human multiple myeloma. Blood 85, 863-872.
    [Google Scholar]
  17. Kyo, S., Inoue, M., Nishio, Y., Nakanishi, K., Akira, S., Inoue, H., Yutsudo, M., Tanizawa, O. & Hakura, A. ( 1993; ). NF-IL6 represses early gene expression of human papillomavirus type 16 through binding to the noncoding region. Journal of Virology 67, 1058-1066.
    [Google Scholar]
  18. Lutticken, C., Wegenka, U. M., Yuan, J., Buschmann, J., Schindler, C., Ziemiecki, A., Harpur, A. G., Wilks, A. F., Yasukawa, K., Taga, T. and others ( 1994; ). Association of transcription factor APRF and protein kinase Jak1 with the interleukin-6 signal transducer gp130. Science 263, 89–92.[CrossRef]
    [Google Scholar]
  19. Malejczyk, J., Malejczyk, M., Urbanski, A., Kock, A., Jablonska, S., Orth, G. & Luger, T. A. ( 1991; ). Constitutive release of IL6 by human papillomavirus type 16 (HPV16)-harboring keratinocytes: a mechanism augmenting the NK-cell-mediated lysis of HPV-bearing neoplastic cells. Cellular Immunology 136, 155-164.[CrossRef]
    [Google Scholar]
  20. Morinaga, Y., Suzuki, H., Takatsuki, F., Akiyama, Y., Taniyama, T., Matsushima, K. & Onozaki, K. ( 1989; ). Contribution of IL-6 to the antiproliferative effect of IL-1 and tumor necrosis factor on tumor cell lines. Journal of Immunology 143, 3538-3542.
    [Google Scholar]
  21. Murakami, M., Hibi, M., Nakagawa, N., Nakagawa, T., Yasukawa, K., Yamanishi, K., Taga, T. & Kishimoto, T. ( 1993; ). IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase. Science 260, 1808-1810.[CrossRef]
    [Google Scholar]
  22. Nakajima, K., Yamanaka, Y., Nakae, K., Kojima, H., Ichiba, M., Kiuchi, N., Kitaoka, T., Fukada, T., Hibi, M. & Hirano, T. ( 1996; ). A central role for Stat3 in IL-6-induced regulation of growth and differentiation in M1 leukemia cells. EMBO Journal 15, 3651-3658.
    [Google Scholar]
  23. Niehof, M., Streetz, K., Rakemann, T., Bischoff, S. C., Manns, M. P., Horn, F. & Trautwein, C. ( 2000; ). Interleukin-6-induced tethering of STAT3 to the LAP/C/EBPbeta promoter suggests a new mechanism of transcriptional regulation by STAT3. Journal of Biological Chemistry 276, 9016-9027.
    [Google Scholar]
  24. Rakemann, T., Niehof, M., Kubicka, S., Fischer, M., Manns, M. P., Rose-John, S. & Trautwein, C. ( 1999; ). The designer cytokine hyper-interleukin-6 is a potent activator of STAT3-dependent gene transcription in vivo and in vitro. Journal of Biological Chemistry 274, 1257-1266.[CrossRef]
    [Google Scholar]
  25. Romano, M., Sironi, M., Toniatti, C., Polentarutti, N., Fruscella, P., Ghezzi, P., Faggioni, R., Luini, W., van Hinsbergh, V., Sozzani, S., Bussolino, F., Poli, V., Ciliberto, G. & Mantovani, A. ( 1997; ). Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity 6, 315-325.[CrossRef]
    [Google Scholar]
  26. Schaefer, T. S., Sanders, L. K. & Nathans, D. ( 1995; ). Cooperative transcriptional activity of Jun and Stat3 beta, a short form of Stat3. Proceedings of the National Academy of Sciences, USA 92, 9097-9101.[CrossRef]
    [Google Scholar]
  27. Schreiber, E., Matthias, P., Muller, M. M. & Schaffner, W. ( 1989; ). Rapid detection of octamer binding proteins with ‘mini-extracts’, prepared from a small number of cells. Nucleic Acids Research 17, 6419.[CrossRef]
    [Google Scholar]
  28. Stahl, N., Boulton, T. G., Farruggella, T., Ip, N. Y., Davis, S., Witthuhn, B. A., Quelle, F. W., Silvennoinen, O., Barbieri, G., Pellegrini, S. and others ( 1994; ). Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6 beta receptor components. Science 263, 92–95.[CrossRef]
    [Google Scholar]
  29. Steger, G. & Corbach, S. ( 1997; ). Dose-dependent regulation of the early promoter of human papillomavirus type 18 by the viral E2 protein. Journal of Virology 71, 50-58.
    [Google Scholar]
  30. Struyk, L., van der Meijden, E., Minnaar, R., Fontaine, V., Meijer, I. & ter Schegget, J. ( 2000; ). Transcriptional regulation of human papillomavirus type 16 LCR by different C/EBPbeta isoforms. Molecular Carcinogenesis 28, 42-50.[CrossRef]
    [Google Scholar]
  31. Taga, T. & Kishimoto, T. ( 1997; ). Gp130 and the interleukin-6 family of cytokines. Annual Review of Immunology 15, 797-819.[CrossRef]
    [Google Scholar]
  32. Taga, T., Hibi, M., Hirata, Y., Yamasaki, K., Yasukawa, K., Matsuda, T., Hirano, T. & Kishimoto, T. ( 1989; ). Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. Cell 58, 573-581.[CrossRef]
    [Google Scholar]
  33. Tamura, T., Udagawa, N., Takahashi, N., Miyaura, C., Tanaka, S., Yamada, Y., Koishihara, Y., Ohsugi, Y., Kumaki, K., Taga, T. and others ( 1993; ). Soluble interleukin-6 receptor triggers osteoclast formation by interleukin 6. Proceedings of the National Academy of Sciences, USA 90, 11924–11928.[CrossRef]
    [Google Scholar]
  34. Zhong, Z., Wen, Z. & Darnell, J. E.Jr. ( 1994; ). Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science 264, 95-98.[CrossRef]
    [Google Scholar]
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