| Expression of AP1 during cellular differentiation determines human papillomavirus E6/E7 expression in stratified epithelial cells. | |
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MedLine Citation:
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PMID: 9018063 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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E6 and E7 oncoproteins of human papillomavirus (HPV) play significant roles in the pathogenesis of cervical cancer. However, the pattern of E6/E7 expression during the productive virus life cycle in differentiating epithelia of the uterine cervix remains unclear. In addition, little is known about the cellular factors regulating E6/E7 expression in differentiating epithelia. In the present study, using transient expression assays and DNA binding assays, we demonstrated that E6/E7 transcription is critically regulated by the cellular factor AP1, a Jun/Fos heterodimer complex. Immunohistochemical analyses of various uterine cervical lesions showed AP1 expression in lower cell layers of normal cervix and low-grade cervical intraepithelial neoplasia (CIN), while it was detected throughout all layers in high-grade CIN and invasive cancer. In situ RNA-RNA hybridization analyses of organotypic raft culture specimens of an HPV-31-containing cell line revealed that E6/E7 transcripts were expressed in most cell layers, with reduced expression in differentiated cells. This pattern of HPV expression correlated with the pattern of AP1 expression detected by immunohistochemical analyses. These findings suggest that E6/E7 expression in differentiating epithelia is dependent on AP1, which appears to be associated with proliferative activity of the cells. Since E6/E7 expression induces cell proliferation, co-expression of AP1 and E6/E7 in undifferentiated cell layers might create a positive regulatory loop, probably contributing to maintenance of initial HPV infection and subsequent activation in basal and suprabasal cell layers. |
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Authors:
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S Kyo; D J Klumpp; M Inoue; T Kanaya; L A Laimins |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: The Journal of general virology Volume: 78 ( Pt 2) ISSN: 0022-1317 ISO Abbreviation: J. Gen. Virol. Publication Date: 1997 Feb |
Date Detail:
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Created Date: 1997-02-24 Completed Date: 1997-02-24 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 0077340 Medline TA: J Gen Virol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 401-11 Citation Subset: IM |
Affiliation:
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Department of Obstetrics and Gynecology, School of Medicine, Kanazawa University, Ishikawa, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Binding Sites Cell Differentiation* Cell Line Cervix Uteri / cytology Enhancer Elements, Genetic Epithelial Cells Epithelium / virology Female Gene Expression Regulation, Viral* Humans Oncogene Proteins, Viral / genetics* Papillomaviridae / genetics*, physiology Protein Binding Proto-Oncogene Proteins c-jun / metabolism Regulatory Sequences, Nucleic Acid Transcription Factor AP-1 / biosynthesis, physiology* Transcription, Genetic |
| Chemical | |
Reg. No./Substance:
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0/Oncogene Proteins, Viral; 0/Proto-Oncogene Proteins c-jun; 0/Transcription Factor AP-1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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