The functionally antagonistic POU family transcription factors Brn-3a and Brn-3b show opposite changes in expression during the growth arrest and differentiation of human neuroblastoma cells.
The Brn-3a and Brn-3b POU family transcription factors have previously been shown to have functionally antagonistic effects, with Brn-3a activating specific gene promoters which are repressed by Brn-3b. We show here that proliferating cell lines of human neuroblastoma origin have a high ratio of Brn-3b to Brn-3a compared with other cell lines derived from related tumours. Moreover, the level of Brn-3a rises and that of Brn-3b falls when neuroblastoma cell lines are exposed to treatments which induce a cessation of proliferation. Such treatments also result in the activation of a test promoter which is normally stimulated by Brn-3a and repressed by Brn-3b. Our findings suggest that these antagonistic factors may play a key role in regulation of gene expression during human neuroblastoma differentiation and could thus represent a potential therapeutic target for treatments designed to induce such differentiation.
Smith
M D
MD
Medical Molecular Biology Unit, Department of Molecular Pathology, University College London Medical School, UK.
Latchman
D S
DS
D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000473:pathology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D013937:Thymidine Kinase / Q000235:genetics; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D050820:Transcription Factor Brn-3B; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C494188:POU4F1 protein, human; C494190:POU4F2 protein, human; D012333:RNA, Messenger; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D050820:Transcription Factor Brn-3B; D014157:Transcription Factors; D013937:Thymidine Kinase