Induction of apoptosis and differentiation in neuroblastoma and astrocytoma cells by the overexpression of Bin1, a novel Myc interacting protein

Bin1 is a novel protein that specifically binds Myc and inhibits, at least in part, Myc transactivation. Bin1 seems to play a role in cell cycle contr ol, acting as a tumor suppressor gene. Since MYC family genes play a regula tory role in the proliferation, differentiation, and apoptosis of the nervo us system, we studied the effects of the overexpression of the Myc-interact ing protein, Bin1, in neuroblastoma and astrocytoma cell lines, which were chosen as neural cell system models. The major effects of BIN1 overexpressi on observed in undifferentiated neuroblastoma and astrocytoma cells were a significant reduction of cell growth, an increased in the G(0)/G(1) cell po pulation and the induction of apoptosis. The trigger of programmed cell dea th by Bin1 is described for the first rime. Bin1 overexpression in undiffer entiated cells did not induce any maturation process as neither neuronal no r astrocyte differentiation markers were upregulated in neuroblastoma and a strocytoma cells, respectively. On the other side, the effects of Bin1 over production in neuroblastoma and astrocytoma cells committed towards neurona l and astrocyte differentiation, respectively, were different from those ob served in undifferentiated cells. Although we did not evidence any triggeri ng of programmed cell death, we did notice a further induction towards more differentiated phenotypes. Our studies suggest that Bin1 overexpression in neuroblastoma and astrocytoma cells can result in one of the following pat hways: (1) suppressed cell proliferation, (2) induced differentiation, or ( 3) apoptosis. Thus, it appears that Bin1 operates through different pathway s that involve activation of different genes: the chosen pathway however wi ll depend on the proliferating or differentiated state of the cell. (C) 199 9 Wiley-Liss, Inc.