Neuroblastomas are the second most common solid
tumor in children but the molecular mechanisms underlying the initiation and progression of this disease are poorly understood. We previously showed that the
Brn-3b transcription factor is highly expressed in actively proliferating
neuroblastoma cells but is significantly decreased when these cells are induced to differentiate. In this study, we analyzed the effects of manipulating Brn-3b levels in the human
neuroblastoma cell line, IMR-32 and showed that constitutive overexpression of Brn-3b consistently increased cellular growth and proliferation in monolayer as well as in an anchorage-independent manner compared with controls whereas stably decreasing Brn-3b can reduce the rate of growth of these cells. Cells with high Brn-3b also fail to respond to growth inhibitory
retinoic acid, as they continue to proliferate. Moreover, Brn-3b levels significantly modified
tumor growth in vivo with elevated Brn-3b resulting in faster
tumor growth in xenograft models whereas decreasing Brn-3b resulted in slower growth compared with controls. Interestingly, elevated Brn-3b levels also enhances the invasive capacity of these
neuroblastoma cells with significantly larger numbers of migrating cells observed in overexpressing clones compared with controls. Because invasion and
metastasis influence morbidity and mortality in
neuroblastoma and so significantly affect the course and outcome of
neuroblastomas, this finding is very important. Our results therefore suggest that
Brn-3b transcription factor contributes to proliferation of
neuroblastoma cells in vivo and in vitro but may also influence progression and/or invasion during
tumorigenesis. It is possible that decreasing Brn-3b levels may reverse some effects on growth and proliferation of these cells.