The Brn-3a transcription factor plays a critical role in regulating human papilloma virus gene expression and determining the growth characteristics of cervical cancer cells.
The Brn-3a POU family transcription factor has previously been shown to activate the human papilloma virus type 16 (HPV-16) promoter driving the expression of the E6- and E7-transforming proteins. Moreover, Brn-3a is overexpressed approximately 300-fold in cervical biopsies from women with cervical intra-epithelial neoplasia type 3 (CIN3) compared with normal cervical material. To test the role of Brn-3a in cervical neoplasia we have manipulated its expression in cervical carcinoma-derived cell lines with or without endogenous HPV genes. In HPV-expressing cells, reduction in Brn-3a expression specifically reduces HPV gene expression, growth rate, saturation density and anchorage-independent growth, whereas these effects are not observed when Brn-3a expression is reduced in cervical cells lacking HPV genomes. Together with our previous observations, these findings indicate a critical role for Brn-3a in regulating HPV gene expression and thereby in controlling the growth/transformation of cervical cells.
Ndisang
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Department of Molecular Pathology, Windeyer Institute of Medical Sciences, University College London, London W1P 6DB, United Kingdom.
Budhram-Mahadeo
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Latchman
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D002455:Cell Division / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D027383:Papillomaviridae / Q000235:genetics*; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D014157:Transcription Factors / Q000502:physiology*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000473:pathology* / Q000821:virology
D004268:DNA-Binding Proteins; C494188:POU4F1 protein, human; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D014157:Transcription Factors; D003907:Dexamethasone