Overexpression of NM23-1 enhances responsiveness of IMR-32 human neuroblastoma cells to differentiation stimuli

Background: Aggressiveness of neuroblastoma is associated with increased expression of the putative metastasis suppressor genes, nm23-1 and nm23-2. These genes encode nucleoside diphosphate kinases A and B that form fr ee or bound homo- and heteromers, which are distributed between soluble and particulate fractions of cells and display catalytic and noncatalytic activities. Materials and Methods: In order to establish which forms and activities of nm23 proteins an operative in neuroblastoma we stably transfected IMR-32 human neuroblastoma cells with constructs encoding wild type and catalytically inactive nm23-1 and nm23-2 proteins. Results: Overexpression of wild type nm23-1 proteins stimulated spontaneous neurite outgrowth and enhanced differentiation in response to se,um starvation and retinoic acid. In contrast, overexpression of the catalytically inactive nm23-1T mutant enhanced TPA-mediated inhibition of differentiation, Conclusion: Our findings suggest that differentiation associated functions of nm23 proteins in IMR-32 neuroblastoma cells are carried out by bound nm23-1 proteins docked in a limited number of nm23-1 specific sites.