Genetic complementation to non‐tumorigenicity in cervical‐carcinoma cells correlates with alterations in AP‐1 composition

• Published in: International journal of cancer 2000-06, Vol.86 (6), p.811-817
• Main Authors: Soto, Ubaldo, Denk, Claudia, Finzer, Patrick, Hutter, Karl‐Josef, zur Hausen, Harald, Rösl, Frank
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Female; Female genital diseases; Genetic Complementation Test; Gynecology. Andrology. Obstetrics; Humans; Medical sciences; Papillomaviridae - isolation & purification; Proto-Oncogene Proteins c-fos - analysis; Transcription Factor AP-1 - analysis; Tumor Cells, Cultured; Tumors; Uterine Cervical Neoplasms - etiology; Uterine Cervical Neoplasms - virology
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(20000615)86:6<811::AID-IJC9>3.0.CO;2-J

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. Int. J. Cancer 86:811–817, 2000. © 2000 Wiley‐Liss, Inc.