This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rösl, F Articles by zur Hausen, H Search for Related Content PubMed PubMed Citation Articles by Rösl, F Articles by zur Hausen, H

 Previous Article  |  Next Article 

J Virol. 1994 April; 68(4): 2142-2150

Differential regulation of the JE gene encoding the monocyte chemoattractant protein (MCP-1) in cervical carcinoma cells and derived hybrids.

Forschungsschwerpunkt Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum, Heidelberg, Germany.

ABSTRACT

Malignant human papillomavirus type 18 (HPV18)-positive cervical carcinoma cells can be reverted to a nonmalignant phenotype by generation of somatic cell hybrids with normal human fibroblasts. Although nontumorigenic hybrids, their tumorigenic segregants, and the parental HeLa cells have similar in vitro properties, inoculation only of nontumorigenic cells into nude mice results in a selective suppression of HPV18 transcription which precedes cessation of cellular growth. Our present study, aimed at understanding the differential regulation in vitro and in vivo, shows that the JE gene, encoding the monocyte chemoattractant protein (MCP-1), is expressed only in nontumorigenic hybrids. Although the gene, including its regulatory region, is intact, no JE (MCP-1) mRNA is detected in the tumorigenic segregants and in other malignant HPV-positive cervical carcinoma cell lines. Tests of several monocyte-derived cytokines showed that only tumor necrosis factor alpha strongly induces the JE (MCP-1) gene in nontumorigenic cells and that this is accompanied by a dose-dependent reduction of HPV transcription. The JE (MCP-1) up-regulation occurs within 2 h and does not require de novo protein synthesis. The response to tumor necrosis factor alpha seems to be mediated by an NF-kappa B-related mechanism, since the induction can be completely abrogated by pretreating the cells with an antioxidant such as pyrrolidine dithiocarbamate. Interestingly, cocultivation of nonmalignant hybrids with monocyte-enriched fractions from human peripheral blood also results in an induction of the JE (MCP-1) gene and a concomitant suppression of HPV18 transcription. Neither effect is observed in malignant cells. These data suggest that JE (MCP-1) may play a pivotal role in the intercellular communication by triggering an intracellular pathway which negatively interferes with viral transcription in HPV-positive nontumorigenic cells.

This article has been cited by other articles:

• Simoes, R. T., Goncalves, M. A. G., Donadi, E. A., Simoes, A. L., Bettini, J. S. R., Duarte, G., Quintana, S. M., Carvalho, M. W. P., Soares, E. G. (2005). Association of Tumor Necrosis Factor a-2 and a-8 Microsatellite Alleles with Human Papillomavirus and Squamous Intraepithelial Lesions among Women in Brazil. J. Clin. Microbiol. 43: 3932-3937 [Abstract] [Full Text]  
• van Riggelen, J., Buchwalter, G., Soto, U., De-Castro Arce, J., Hausen, H. z., Wasylyk, B., Rosl, F. (2005). Loss of Net as Repressor Leads to Constitutive Increased c-fos Transcription in Cervical Cancer Cells. J. Biol. Chem. 280: 3286-3294 [Abstract] [Full Text]  
• Bachmann, A., Hanke, B., Zawatzky, R., Soto, U., van Riggelen, J., zur Hausen, H., Rosl, F. (2002). Disturbance of Tumor Necrosis Factor Alpha-Mediated Beta Interferon Signaling in Cervical Carcinoma Cells. J. Virol. 76: 280-291 [Abstract] [Full Text]  
• Lakics, V., Medvedev, A. E., Okada, S., Vogel, S. N. (2000). Inhibition of LPS-induced Cytokines by Bcl-xL in a Murine Macrophage Cell Line. J. Immunol. 165: 2729-2737 [Abstract] [Full Text]  
• Hess, S., Smola, H., Sandaradura de Silva, U., Hadaschik, D., Kube, D., Baldus, S. E., Flucke, U., Pfister, H. (2000). Loss of IL-6 Receptor Expression in Cervical Carcinoma Cells Inhibits Autocrine IL-6 Stimulation: Abrogation of Constitutive Monocyte Chemoattractant Protein-1 Production. J. Immunol. 165: 1939-1948 [Abstract] [Full Text]  
• Hausen, H. z. (2000). Papillomaviruses Causing Cancer: Evasion From Host-Cell Control in Early Events in Carcinogenesis. JNCI J Natl Cancer Inst 92: 690-698 [Abstract] [Full Text]  
• Altenburg, A., Baldus, S. E., Smola, H., Pfister, H., Hess, S. (1999). CD40 Ligand-CD40 Interaction Induces Chemokines in Cervical Carcinoma Cells in Synergism with IFN-{gamma}. J. Immunol. 162: 4140-4147 [Abstract] [Full Text]  
• Tsao, P. S., Niebauer, J., Buitrago, R., Lin, P. S., Wang, B.-y., Cooke, J. P., Ida Chen, Y-d., Reaven, G. M. (1998). Interaction of Diabetes and Hypertension on Determinants of Endothelial Adhesiveness. Arterioscler. Thromb. Vasc. Bio. 18: 947-953 [Abstract] [Full Text]