Soluble interleukin-6 receptor activates the human papillomavirus type 18 long control region in SW756 cervical carcinoma cells in a STAT3-dependent manner.
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/EBPbeta) was induced only as a late event. While C/EBPbeta 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.
Smola-Hess
Sigrun
S
Institute of Virology, University of Cologne, Fürst-Pückler-Str. 56, D-50935 Cologne, Germany1.
Sandaradura de Silva
Ute
U
Institute of Virology, University of Cologne, Fürst-Pückler-Str. 56, D-50935 Cologne, Germany1.
Hadaschik
Dirk
D
Institute of Virology, University of Cologne, Fürst-Pückler-Str. 56, D-50935 Cologne, Germany1.
Pfister
Herbert J
HJ
Institute of Virology, University of Cologne, Fürst-Pückler-Str. 56, D-50935 Cologne, Germany1.
D022782:CCAAT-Enhancer-Binding Protein-beta / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology; D027383:Papillomaviridae / Q000235:genetics*; D011401:Promoter Regions, Genetic; D019947:Receptors, Interleukin-6 / Q000502:physiology*; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000502:physiology*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000821:virology*
D022782:CCAAT-Enhancer-Binding Protein-beta; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators