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


CONCLUSIONS
BIN1 inactivation may be necessary for MYCN overexpression to lead to cellular proliferation rather than programmed cell death in neuroblastomas with MYCN amplification.
Hogarty
M D
MD
Department of Pediatrics, University of Pennsylvania School of Medicine and The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104-4318, USA. hogartym@email.chop.edu
Liu
X
X
Thompson
P M
PM
White
P S
PS
Sulman
E P
EP
Maris
J M
JM
Brodeur
G M
GM
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002455:Cell Division; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D048868:Adaptor Proteins, Signal Transducing; C101410:BIN1 protein, human; D002352:Carrier Proteins; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins