Loss of net as repressor leads to constitutive increased c-fos transcription in cervical cancer cells

Jan Van Riggelen, Gilles Buchwalter, Ubaldo Soto, Johanna De-Castro Arce, Harald Zur Hausen, Bohdan Wasylyk, Frank Rösl

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)3286-3294
Number of pages9
JournalJournal of Biological Chemistry
Volume280
Issue number5
DOIs
StatePublished - Feb 4 2005

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Van Riggelen, J., Buchwalter, G., Soto, U., De-Castro Arce, J., Zur Hausen, H., Wasylyk, B., & Rösl, F. (2005). Loss of net as repressor leads to constitutive increased c-fos transcription in cervical cancer cells. Journal of Biological Chemistry, 280(5), 3286-3294. https://doi.org/10.1074/jbc.M409915200