nm23 influences proliferation and differentiation of PC12 cells in response to nerve growth factor

The nm23 genes codify nucleoside diphosphate kinases, which have been shown to be involved in the regulation of microtubule dynamics. We have demonstrated previously that the association between the Nm23-M1 protein and cytoskeletal beta-tubulin correlates with cell differentiation. It is known that microtubules and microtubule-associated proteins are fundamental elements regulating neuronal differentiation. In the present study, we have investigated the ability of nm23 to influence nerve growth factor-induced PC12 cell differentiation. To this end, we have altered PC12 intracellular levels of nm23-M1 by means of sense and antisense transfections. In the presence of nerve growth factor, overexpression of nm23 delays cell cycle transition, rapidly induces neurite outgrowth, and increases the expression of neurofilament and microtubule proteins. On the contrary, down-regulation of nm23 enhances cell proliferation and inhibits neuronal differentiation. These findings indicate that neuronal cell proliferation and differentiation can be modulated by nm23 expression levels.