THE RB-RELATED GENE RB2 P130 IN NEUROBLASTOMA-DIFFERENTIATION AND IN B-MYB PROMOTER DOWN-REGULATION/

The retinoblastoma family of nuclear factors is composed of RE, the pr ototype of the tumour suppressor genes and of the strictly related gen es p107 and Rb2/p130. The three genes code for proteins, namely pRb, p 107 and pRb2/p130, that share similar structures and functions. These proteins are expressed, often simultaneously, in many cell types and a re involved in the regulation of proliferation and differentiation. We determined the expression and the phosphorylation of the RE family ge ne products during the DMSO-induced differentiation of the N1E-115 mur ine neuroblastoma cells. In this system, pRb2/p130 was strongly up-reg ulated during mid-late differentiation stages, white, on the contrary, pRb and p107 resulted markedly decreased at late stages. Differentiat ing N1E-115 cells also showed a progressive decrease in B-myb levels, a proliferation-related protein whose constitutive expression inhibits neuronal differentiation. Transfection of each of the RE family genes in these cells was able, at different degrees, to induce neuronal dif ferentiation, to inhibit [H-3]thymidine incorporation and to down-regu late the activity of the B-myb promoter.