Interplay between the antimetastatic nm23 and the Retinoblastoma-related Rb2/p130 genes in promoting neuronal differentiation of PC12 cells

Increasing evidence indicates that the nm23 genes, initially documented as suppressors of metastasis progression, are involved in normal development a nd differentiation. We have shown previously that the murine nm23 gene enha nces pheochromocytoma PC12 cells responsiveness to NGF by accelerating cell growth arrest and neurite outgrowth, The present study was aimed at elucid ating the mechanisms by which nm23 controls cell proliferation and promotes neuronal differentiation, We demonstrated that nm23 modulates the expressi on of the Rb2/p130 gene, a negative regulator of cell cycle progression als o implicated in the maintenance of the differentiated state, Furthermore, w e showed that nm23-H1 mutants, defective in inhibiting the invasive phenoty pe, downregulate Rb2/p130 expression and inhibit NGF-induced pC12 cell diff erentiation. in synthesis, our results provide first evidence of Interplay between the nm23 and the Rb2/p130 genes in driving PC12 cells neuronal diff erentiation and suggest that the antimetastatic and the differentiative nm2 3 functions can have similar features.