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

Med Pediatr Oncol. 2000 Dec;35(6):559-62. doi: 10.1002/1096-911x(20001201)35:6<559::aid-mpo14>3.0.co;2-j.

Abstract

Background: MYCN amplification and overexpression occurs in 25% of neuroblastomas and independently predicts for poor prognosis disease, an effect thought to be mediated by its role as a transcriptional activator of growth promoting genes. However, in many mammalian cells, deregulated expression of MYC family genes (including MYCN) induces apoptosis. We hypothesized that BIN1, a MYC interacting protein capable of inducing apoptosis, may be an important 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-copy, cell lines. This effect appeared to be caused by an increase in apoptosis, and was augmented by serum deprivation and concurrent cytotoxic drug therapy in cell culture

Conclusion: BIN1 inactivation may be necessary for MYCN overexpression to lead to cellular proliferation rather than programmed cell death in neuroblastomas with MYCN amplification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Apoptosis / genetics*
  • Carrier Proteins / genetics*
  • Cell Division
  • Gene Expression Regulation, Neoplastic*
  • Genes, Tumor Suppressor / genetics*
  • Genes, myc / genetics*
  • Humans
  • Neuroblastoma / genetics*
  • Neuroblastoma / pathology
  • Nuclear Proteins / genetics*
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins*

Substances

  • Adaptor Proteins, Signal Transducing
  • BIN1 protein, human
  • Carrier Proteins
  • Nuclear Proteins
  • Tumor Suppressor Proteins