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 free or bound homo- and heteromers, which are distributed between soluble and particulate fractions of cells and display catalytic and non-catalytic activities.


METHODS
In order to establish which forms and activities of nm23 proteins are 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 serum starvation and retinoic acid. In contrast, overexpression of the catalytically inactive nm23-1T mutant enhanced TPA-mediated inhibition of differentiation.


CONCLUSIONS
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.
Backer
M V
MV
SibTech, Inc., Newington, CT 06111, USA. mbacker@sibtech.com
Kamel
N
N
Sandoval
C
C
Jayabose
S
S
Mendola
C E
CE
Backer
J M
JM
D000970:Antineoplastic Agents / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D054778:NM23 Nucleoside Diphosphate Kinases; D016501:Neurites / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D009701:Nucleoside-Diphosphate Kinase; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D054778:NM23 Nucleoside Diphosphate Kinases; D014157:Transcription Factors; D014212:Tretinoin; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate