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/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.
AkiraS.,
IsshikiH.,
SugitaT.,
TanabeO.,
KinoshitaS.,
NishioY.,
NakajimaT.,
HiranoT.,
KishimotoT.1990; A nuclear factor for IL-6 expression (NF-IL6) is a member of a C/EBP family. EMBO Journal 9:1897–1906
AltenburgA.,
BaldusS. E.,
SmolaH.,
PfisterH.,
HessS.1999; CD40 ligand–CD40 interaction induces chemokines in cervical carcinoma cells in synergism with IFN-gamma. Journal of Immunology 162:4140–4147
BauknechtT.,
SeeR. H.,
ShiY.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
BaumannH.,
MorellaK. K.,
CamposS. P.,
CaoZ.,
JahreisG. 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
BoultonT. G.,
StahlN.,
YancopoulosG. 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
ChenL.,
MoryY.,
ZilbersteinA.,
RevelM.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
DaeipourM.,
KumarG.,
AmaralM. C.,
NelA. 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
HessS.,
SmolaH.,
Sandaradura De SilvaU.,
HadaschikD.,
KubeD.,
BaldusS. E.,
FluckeU.,
PfisterH.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
HibiM.,
MurakamiM.,
SaitoM.,
HiranoT.,
TagaT.,
KishimotoT.1990; Molecular cloning and expression of an IL-6 signal transducer, gp130. Cell 63:1149–1157
HiranoT.,
IshiharaK.,
HibiM.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
KyoS.,
InoueM.,
NishioY.,
NakanishiK.,
AkiraS.,
InoueH.,
YutsudoM.,
TanizawaO.,
HakuraA.1993; NF-IL6 represses early gene expression of human papillomavirus type 16 through binding to the noncoding region. Journal of Virology 67:1058–1066
LuttickenC.,
WegenkaU. M.,
YuanJ.,
BuschmannJ.,
SchindlerC.,
ZiemieckiA.,
HarpurA. G.,
WilksA. F.,
YasukawaK.,
TagaT.and others1994; Association of transcription factor APRF and protein kinase Jak1 with the interleukin-6 signal transducer gp130. Science 263:89–92
MalejczykJ.,
MalejczykM.,
UrbanskiA.,
KockA.,
JablonskaS.,
OrthG.,
LugerT. 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
MorinagaY.,
SuzukiH.,
TakatsukiF.,
AkiyamaY.,
TaniyamaT.,
MatsushimaK.,
OnozakiK.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
NakajimaK.,
YamanakaY.,
NakaeK.,
KojimaH.,
IchibaM.,
KiuchiN.,
KitaokaT.,
FukadaT.,
HibiM.,
HiranoT.1996; A central role for Stat3 in IL-6-induced regulation of growth and differentiation in M1 leukemia cells. EMBO Journal 15:3651–3658
NiehofM.,
StreetzK.,
RakemannT.,
BischoffS. C.,
MannsM. P.,
HornF.,
TrautweinC.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
RakemannT.,
NiehofM.,
KubickaS.,
FischerM.,
MannsM. P.,
Rose-JohnS.,
TrautweinC.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
RomanoM.,
SironiM.,
ToniattiC.,
PolentaruttiN.,
FruscellaP.,
GhezziP.,
FaggioniR.,
LuiniW.,
van HinsberghV.,
SozzaniS.,
BussolinoF.,
PoliV.,
CilibertoG.,
MantovaniA.1997; Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity 6:315–325
SchaeferT. S.,
SandersL. K.,
NathansD.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
SchreiberE.,
MatthiasP.,
MullerM. M.,
SchaffnerW.1989; Rapid detection of octamer binding proteins with ‘mini-extracts’, prepared from a small number of cells. Nucleic Acids Research 17:6419
StahlN.,
BoultonT. G.,
FarruggellaT.,
IpN. Y.,
DavisS.,
WitthuhnB. A.,
QuelleF. W.,
SilvennoinenO.,
BarbieriG.,
PellegriniS.and others1994; Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6 beta receptor components. Science 263:92–95
StegerG.,
CorbachS.1997; Dose-dependent regulation of the early promoter of human papillomavirus type 18 by the viral E2 protein. Journal of Virology 71:50–58
StruykL.,
van der MeijdenE.,
MinnaarR.,
FontaineV.,
MeijerI.,
ter ScheggetJ.2000; Transcriptional regulation of human papillomavirus type 16 LCR by different C/EBPbeta isoforms. Molecular Carcinogenesis 28:42–50
TagaT.,
HibiM.,
HirataY.,
YamasakiK.,
YasukawaK.,
MatsudaT.,
HiranoT.,
KishimotoT.1989; Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. Cell 58:573–581
TamuraT.,
UdagawaN.,
TakahashiN.,
MiyauraC.,
TanakaS.,
YamadaY.,
KoishiharaY.,
OhsugiY.,
KumakiK.,
TagaT.and others1993; Soluble interleukin-6 receptor triggers osteoclast formation by interleukin 6. Proceedings of the National Academy of Sciences, USA 90:11924–11928
ZhongZ.,
WenZ.,
DarnellJ.E.Jr1994; Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science 264:95–98
Soluble interleukin-6 receptor activates the human papillomavirus type 18 long control region in SW756 cervical carcinoma cells in a STAT3-dependent manner