TY - JOUR
T1 - Loss of net as repressor leads to constitutive increased c-fos transcription in cervical cancer cells
AU - Van Riggelen, Jan
AU - Buchwalter, Gilles
AU - Soto, Ubaldo
AU - De-Castro Arce, Johanna
AU - Zur Hausen, Harald
AU - Wasylyk, Bohdan
AU - Rösl, Frank
PY - 2005/2/4
Y1 - 2005/2/4
N2 - We have investigated the expression of c-fos in cervical carcinoma cells and in somatic cell hybrids derived therefrom. In malignant cells, c-fos was constitutively expressed even after serum starvation. Dissection of the c-fos promoter showed that expression was mainly controlled by the SRE motif, which was active in malignant cells, but repressed in their non-malignant counterparts. Constitutive SRE activity was not mediated by sustained mitogen-activated protein kinase activity but because of inefficient expression of the ternary complex factor Net, which was either very low or even barely discernible. Chromatin immunoprecipitation assays revealed that Net directly binds to the SRE nucleoprotein complex in non-tumorigenic cells, but not in malignant segregants. Small interfering RNA targeted against Net resulted in enhanced c-fos transcription, clearly illustrating its repressor function. Conversely, stable ectopic expression of Net in malignant cells negatively regulated endogenous c-fos, resulting in a disappearance of the c-Fos protein from the AP-1 transcription complex. These data indicate that loss of Net and constitutive c-fos expression appear to be a key event in the transformation of cervical cancer cells.
AB - We have investigated the expression of c-fos in cervical carcinoma cells and in somatic cell hybrids derived therefrom. In malignant cells, c-fos was constitutively expressed even after serum starvation. Dissection of the c-fos promoter showed that expression was mainly controlled by the SRE motif, which was active in malignant cells, but repressed in their non-malignant counterparts. Constitutive SRE activity was not mediated by sustained mitogen-activated protein kinase activity but because of inefficient expression of the ternary complex factor Net, which was either very low or even barely discernible. Chromatin immunoprecipitation assays revealed that Net directly binds to the SRE nucleoprotein complex in non-tumorigenic cells, but not in malignant segregants. Small interfering RNA targeted against Net resulted in enhanced c-fos transcription, clearly illustrating its repressor function. Conversely, stable ectopic expression of Net in malignant cells negatively regulated endogenous c-fos, resulting in a disappearance of the c-Fos protein from the AP-1 transcription complex. These data indicate that loss of Net and constitutive c-fos expression appear to be a key event in the transformation of cervical cancer cells.
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U2 - 10.1074/jbc.M409915200
DO - 10.1074/jbc.M409915200
M3 - Article
C2 - 15548518
AN - SCOPUS:13544275018
SN - 0021-9258
VL - 280
SP - 3286
EP - 3294
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 5
ER -