Brn-3a and Brn-3b are closely related members of the POU family of transcription factors which have opposite effects on the activity of target promoters. When mouse or human neuroblastoma cells are induced to differentiate to a non-dividing phenotype bearing numerous neuronal processes, the levels of Brn-3a rise dramatically whilst Brn-3b levels fall. Inhibition of Brn-3a expression using an antisense approach or over-expression of Brn-3b, prevents the differentiation of neuroblastoma cells in response to stimuli which normally induce it. Conversely, over-expression of Brn-3a induces differentiation in the absence of such stimuli. Hence the balance between Brn-3a and Brn-3b plays a key role in regulating neuroblastoma differentiation via the activation by Brn-3a or repression by Brn-3b of specific genes whose protein products are required for this process.

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