N-myc down regulates neural cell adhesion molecule expression in rat neuroblastoma.
In human neuroblastoma, amplification of the N-myc oncogene is correlated with increased metastatic ability. We recently showed that transfection of the rat neuroblastoma cell line B104 with an N-myc expression vector resulted in an increase in metastatic ability and a significant reduction in the expression of major histocompatibility complex class I antigens. We examined whether N-myc causes additional phenotypic changes in these cells. We showed that expression of N-myc leads to a dramatic reduction in the levels of neural cell adhesion molecule (NCAM) polypeptides and mRNAs. Spontaneous revertants of the high N-myc phenotype were found to have regained significant levels of NCAM expression, indicating that the continued expression of N-myc is required to maintain the low NCAM phenotype. NCAM was not reduced in B104 cells transfected with the neomycin resistance vector alone, and other neuronal markers were not specifically reduced in N-myc-transfected B104 cells. As NCAM functions in cell-cell adhesion, decreased NCAM expression could contribute significantly to the increased metastatic potential of N-myc-amplified neuroblastomas.
Akeson
R
R
Division of Basic Research, Children's Hospital, Cincinnati, Ohio 45229.
Bernards
R
R
D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D008970:Molecular Weight; D009447:Neuroblastoma / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D014162:Transfection
D015816:Cell Adhesion Molecules, Neuronal; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger