The Brn-3a transcription factor plays a key role in regulating the growth of cervical cancer cells in vivo.
The cellular Brn-3a transcription factor is known to activate transcription of the genes encoding the human papilloma virus E6 and E7 proteins and is over-expressed in women with cervical neoplasia. We show that cervical cell lines with reduced Brn-3a expression show a greatly reduced ability to form tumours in nude mice compared to control cells and also show reduced expression of the HPV E6 and cellular Bcl-2 oncogenes. These effects are also observed in cervical cells over-expressing the related Brn-3b factor, which is known to antagonize activation of HPV gene expression by Brn-3a. These results demonstrate, for the first time, that inhibition of Brn-3a expression or enhanced Brn-3b expression can inhibit cervical cell-derived tumour growth in vivo as well as in vitro. Hence they establish Brn-3a as a key factor in cervical tumorigenesis and as a potential therapeutic target in human cervical neoplasia.
Ndisang
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D
Medical Molecular Biology Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
Budhram-Mahadeo
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V
Pedley
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B
Latchman
D S
DS
D002455:Cell Division; D004268:DNA-Binding Proteins / Q000032:analysis / Q000502:physiology*; D005260:Female; D006801:Humans; D027383:Papillomaviridae / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D050820:Transcription Factor Brn-3B; D014157:Transcription Factors / Q000032:analysis / Q000502:physiology*; D002583:Uterine Cervical Neoplasms / Q000473:pathology* / Q000821:virology
D004268:DNA-Binding Proteins; C494188:POU4F1 protein, human; C494190:POU4F2 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D050820:Transcription Factor Brn-3B; D014157:Transcription Factors