Bcl-2 and M-Myc coexpression increases IGF-IR and features of malignant growth in neuroblastoma cell lines.
The bcl-2 and c-myc oncogenes cooperate to transform multiple cell types. In the pediatric malignancy NB(2), Bcl-2 is highly expressed. In tumors with a poor prognosis, N-Myc, a protein homologous to c-Myc, is overexpressed as a result of gene amplification. The present study was designed to determine whether Bcl-2 cooperates with N-Myc to bestow a tumorigenic phenotype to neuroblastoma (NB) cells. NB cell lines that at baseline express neither Bcl-2 nor N-Myc were stably transfected to express these gene products. In this model, we found Bcl-2 rescues N-Myc-expressing cells from apoptosis induced by serum withdrawal. Coexpression of Bcl-2 and N-Myc supports growth in low serum conditions and anchorage-independent growth in soft agar. Similarly, in vivo tumorigenic and angiogenic activity was dependent on coexpression. Our data further suggests that the mechanism underlying these changes involves the receptor for insulin growth factor type I (IGF-IR).
Jasty
R
R
Department of Pediatrics, Medical College of Ohio, Toledo, OH 43614, USA.
van Golen
C
C
Lin
H J
HJ
Solomon
G
G
Heidelberger
K
K
Polverini
P
P
Opipari
A
A
Feldman
E
E
Castle
V P
VP
D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion; D002455:Cell Division; D002470:Cell Survival; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000378:metabolism
D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017526:Receptor, IGF Type 1