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

Background, The expression of several genes is modulated during neuroblasto ma 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 fo und that, in neuroblastoma cell lines, pRb and p107 proteins decreased, und ergoing progressive de-phosphorylation, whereas pR62/p130 increased at late stages of differentiation. B-myb expression was down-regulated in associat ion with the up-regulation of pR62/p130, the major partner of E2F on the E2 F site of the B-myb promoter in differentiated cells. Transfection of each of the retinoblastoma family genes in neuroblastoma cells was able to induc e neural differentiation, to inhibit H-3-thymidine incorporation, and to do wn-regulate E-myb promoter activity. Conclusions. In conclusion, our data s uggest a major contribution of retinoblastoma proteins, and especially of p R62/p130, in B-myb promoter regulation and demonstrate the induction of neu ral differentiation by p107 and pR62/p130, suggesting a role of these prote ins in triggering differentiation-specific genes. Med. Pediatr. Oncol. 36:1 04-107, 2001. (C) 2001 Wiley-Liss. Inc.