c-myb down regulation is associated with apoptosis in human neuroblastoma cells.

The c-myb transcriptional regulator plays a crucial role in the control of several proliferative/differentiative processes in haematopoietic cells. Its expression and function is not lineage-restricted, since c-myb is also expressed in solid tumours such as neuroblastomas, where its transcription is decreased by retinoic acid. In response to retinoic acid, neuroblastomas differentiate either towards a neuronal phenotype or undergo apoptosis. The temporal relationship between reduction in c-myb mRNA levels and the differentiative/proliferative/apoptotic processes suggests that c-myb may play a key role in the control of growth of these neuroectodermal tumours. Transfection of neuroblastoma cells with expression vectors containing segments of human c-myb cDNA in antisense orientation yielded fewer transfectant clones, with a far slower proliferation rate, than transfection with the corresponding sense construct. The dramatic growth arrest and reduction in cell number in the antisense transfectants is due to the induction of apoptosis. Apoptosis in the c-myb antisense-transfected cells is further increased in reduced serum conditions.