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 and differentiation. We have shown previously that the murine nm23 gene enhances pheochromocytoma PC12 cells responsiveness to NGF by accelerating cell growth arrest and neurite outgrowth. The present study was aimed at elucidating the mechanisms by which nm23 controls cell proliferation and promotes neuronal differentiation. We demonstrated that nm23 modulates the expression of the Rb2/p130 gene, a negative regulator of cell cycle progression also implicated in the maintenance of the differentiated state. Furthermore, we showed that nm23-H1 mutants, defective in inhibiting the invasive phenotype, downregulate Rb2/p130 expression and inhibit NGF-induced PC12 cell differentiation. In synthesis, our results provide first evidence of interplay between the nm23 and the Rb2/p130 genes in driving PC12 cells neuronal differentiation and suggest that the antimetastatic and the differentiative nm23 functions can have similar features.
Lombardi
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Department of Experimental Medicine, University of L'Aquila, Via Vetoio, Coppito 2, 67100 L'Aquila, Italy. lombardi@ifo.it
Palescandolo
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E
Giordano
A
A
Paggi
M G
MG
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D005786:Gene Expression Regulation; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D054778:NM23 Nucleoside Diphosphate Kinases; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D009701:Nucleoside-Diphosphate Kinase; D016716:PC12 Cells; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011506:Proteins; D016372:RNA, Antisense / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein / Q000378:metabolism; D050717:Retinoblastoma-Like Protein p130; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D054778:NM23 Nucleoside Diphosphate Kinases; D010750:Phosphoproteins; D011506:Proteins; D016372:RNA, Antisense; C493839:Rbl2 protein, rat; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein; D050717:Retinoblastoma-Like Protein p130; D014157:Transcription Factors; D020932:Nerve Growth Factor; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins