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. Procedure and Results. In this study, we found that, in neuroblastoma cell lines, pRb and p107 proteins decreased, undergoing progressive de-phosphorylation, whereas pR62/p130 increased at late stages of differentiation. B-myb expression was down-regulated in association with the up-regulation of pR62/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 H-3-thymidine incorporation, and to down-regulate E-myb promoter activity. Conclusions. In conclusion, our data suggest a major contribution of retinoblastoma proteins, and especially of pR62/p130, in B-myb promoter regulation and demonstrate the induction of neural differentiation by p107 and pR62/p130, suggesting a role of these proteins in triggering differentiation-specific genes. Med. Pediatr. Oncol. 36:104-107, 2001. (C) 2001 Wiley-Liss. Inc.