RB2/p130 ectopic gene expression in neuroblastoma stem cells: evidence of cell-fate restriction and induction of differentiation.
The activity of the RB2/p130 gene, which is a member of the retinoblastoma gene family, is cell-cycle-regulated and plays a key role in growth inhibition and differentiation. We used neuroblastoma cell lines as a model for studies on neural crest progenitor cell differentiation. We show that Rb2/p130 ectopic protein expression induces morphological and molecular modifications, promoting differentiation of intermediate (I) phenotype SK-N-BE(2)-C neuroblastoma cells towards a neuroblastic (N) rather than a Schwann/glial/melanocytic (S) phenotype. These modifications are stable as they persist even after treatment with an S-phenotype inducer. Rb2/p130 ectopic expression also induces a more differentiated phenotype in N-type SH-SY-5Y cells. Further, this function appears to be independent of cell-cycle withdrawal. The data reported suggest that the Rb2/p130 protein is able to induce neuronal lineage specification and differentiation in neural crest stem and committed neuroblastoma cells, respectively. Thus, the Rb2/p130 protein seems to be required throughout the full neural maturation process.
Jori
F P
FP
Department of Neurological Sciences, Second University of Naples, Via Pansini 5, 80100 Naples, Italy.
Galderisi
U
U
Piegari
E
E
Peluso
G
G
Cipollaro
M
M
Cascino
A
A
Giordano
A
A
Melone
M A
MA
D001798:Blood Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division; D002460:Cell Line; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007668:Kidney; D005810:Multigene Family; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D011506:Proteins; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis; D050717:Retinoblastoma-Like Protein p130; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D001798:Blood Proteins; D018797:Cell Cycle Proteins; D011506:Proteins; C493837:RBL2 protein, human; D012333:RNA, Messenger; D011994:Recombinant Proteins; D050717:Retinoblastoma-Like Protein p130