Overexpression of BETA2/NeuroD induces neurite outgrowth in F11 neuroblastoma cells

BETA2/NeuroD, a basic helix-loop-helix (bHLH) transcription factor, has bee n shown to play important roles in the development of the nervous system an d the maintenance and formation of pancreatic and enteroendocrine cells. Th e gain of function of BETA2/NeuroD in neurogenesis has been shown in Xenopu s embryos. In this study, we investigated the neurogenic potential of BETA2 /NeuroD using neuroblastoma cell line, F11, which could be induced to diffe rentiate into neurons in the presence of cAMP. To induce or block the expre ssion of BETA2/NeuroD, expression vectors for the full-length and a C-termi nal deletion mutant of BETA2 were constructed and their transactivation pot ential was verified using reporter genes containing the insulin promoter se quences. Overexpression of BETA2 with full-length construct induced neurite outgrowth in F11 cells in the absence of cAMP. In contrast, the C-terminal deletion BETA2(1-233), which has dominant negative activity, inhibited neu rite outgrowth induced by CAMP in F11 cells. These results indicate that BE TA2/NeuroD plays an important role in terminal differentiation of neuroblas toma cells. They also imply that BETA2/NeuroD or related bHLH factors plays an essential role for differentiation of F11 neuroblastoma cells.