Retinoblastoma family proteins induce differentiation and regulate B-myb expression in neuroblastoma cells.
BACKGROUND
The expression of several genes is modulated during neuroblastoma differentiation. The retinoblastoma family proteins, pRb, p107 and pRb2/p130, act in the repression of proliferation genes, interacting mainly with the E2F transcription factors.


RESULTS
In this study, we found that, in neuroblastoma cell lines, pRb and p107 proteins decreased, undergoing progressive dephosphorylation, whereas pRb2/p130 increased at late stages of differentiation. B-myb expression was down-regulated in association with the up-regulation of pRb2/p130, the major partner of E2F on the E2F site of the B-myb promoter in differentiated cells. Transfection of each of the retinoblastoma family genes in neuroblastoma cells was able to induce neural differentiation, to inhibit 3H-thymidine incorporation, and to down-regulate B-myb promoter activity.


CONCLUSIONS
In conclusion, our data suggest a major contribution of retinoblastoma proteins, and especially of pRb2/p130, in B-myb promoter regulation and demonstrate the induction of neural differentiation by p107 and pRb2/p130, suggesting a role of these proteins in triggering differentiation-specific genes.
Raschellà
G
G
ENEA, CR Casaccia, Section of Toxicology and Biomedical Sciences, Rome, Italy. raschella@casaccia.enea.it
Tanno
B
B
Bonetto
F
F
Negroni
A
A
Amendola
R
R
Paggi
M G
MG
D000818:Animals; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D050684:E2F Transcription Factors; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D016161:Genes, Retinoblastoma; D020570:Genes, myb; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011506:Proteins; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D016160:Retinoblastoma Protein / Q000502:physiology*; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D015534:Trans-Activators / Q000096:biosynthesis*; D014157:Transcription Factors / Q000502:physiology; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; C064352:MYBL2 protein, human; C499306:Mybl2 protein, mouse; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; C493844:RBL1 protein, human; C493837:RBL2 protein, human; C489485:Rbl1 protein, mouse; C493838:Rbl2 protein, mouse; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D015534:Trans-Activators; D014157:Transcription Factors; D014212:Tretinoin; D008156:Luciferases; D004121:Dimethyl Sulfoxide