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Retinoblastoma family proteins induce differentiation and regulate B-myb expression in neuroblastoma cells

✍ Scribed by Raschell�, Giuseppe ;Tanno, Barbara ;Bonetto, Francesco ;Negroni, Anna ;Amendola, Roberto ;Paggi, Marco G.

Publisher
John Wiley and Sons
Year
2001
Tongue
English
Weight
278 KB
Volume
36
Category
Article
ISSN
0098-1532

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✦ Synopsis

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. Procedure and 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 3 H-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 Bmyb 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. Med. Pediatr. Oncol. 36:104-107, 2001.

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