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| Home > Publications database > Genetic complementation to non-tumorigenicity in cervical-carcinoma cells correlates with alterations in AP-1 composition. |
| Home > Publications database > Genetic complementation to non-tumorigenicity in cervical-carcinoma cells correlates with alterations in AP-1 composition. |
| Journal Article | DKFZ-2023-01899 |
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2000
Wiley-Liss
Bognor Regis
Abstract: The transcription factor AP-1 represents a central key element in the expression of human pathogenic papillomaviruses (HPV). We here propose a novel role for AP-1 as an essential component of an intracellular surveillance mechanism negatively controlling the proliferation of HPV-positive cells under in vivo conditions. The dissection of AP-1 composition in cervical-carcinoma cells revealed an inverse relationship between the Fos-related antigen Fra-1 and the tumorigenic phenotype. Cervical-carcinoma cell lines were either negative or expressed only low amounts of Fra-1 (jointly with c-Fos) within their AP-1 complexes. Somatic-cell hybridization technique was used to fuse different HPV-positive malignant cell lines. This resulted either in tumorigenic hybrids or in cells in which the malignant phenotype of the parental fusion partners was completely suppressed. The monitoring of AP-1 composition in electrophoretic mobility super-shift assays showed that the amount of Fra-1 was substantially increased within the AP-1 complex of non-malignant cells. In contrast, Fra-1 was even diminished in malignant hybrids, while c-Fos remained expressed. This correlation suggests that the concentration of Fra-1 within the AP-1 transcription complex might be an important marker for predicting the in vivo growth properties of HPV-positive cells.
Keyword(s): Female (MeSH) ; Genetic Complementation Test (MeSH) ; Humans (MeSH) ; Papillomaviridae: isolation & purification (MeSH) ; Proto-Oncogene Proteins c-fos: analysis (MeSH) ; Transcription Factor AP-1: analysis (MeSH) ; Tumor Cells, Cultured (MeSH) ; Uterine Cervical Neoplasms: etiology (MeSH) ; Uterine Cervical Neoplasms: virology (MeSH) ; Proto-Oncogene Proteins c-fos ; Transcription Factor AP-1 ; fos-related antigen 1
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