BIN1 inhibits colony formation and induces apoptosis in neuroblastoma celllines with MYCN amplification

Background. MYCN amplification and overexpression occurs in 25% of neurobla stomas and independently predicts for poor prognosis disease, an effect tho ught to be mediated by its role as a transcriptional activator of growth pr omoting genes. However, in many mammalian cells, deregulated expression of MYC family genes including MYCM induces apoptosis. We hypothesized that BIN 1, a MYC interacting protein capable of inducing apoptosis, may be an impor tant regulator of MYCN in neuroblastoma. Results. BIN1 expression was found to be reduced in MYCN-amplified cell lines. Further, forced expression of BIN1 markedly reduced colony formation in MYCN-amplified, but not single-co py, cell lines. This effect appeared to be caused by an increase in apoptos is, and was augmented by serum deprivation and concurrent cytotoxic drug th erapy in cell culture Conclusion. BIN1 inactivation may be necessary for MY CN overexpression to lead to cellular proliferation rather than programmed cell death in neuroblastomas with MYCN amplification. (C) 2000 Wiley-Liss, Inc.