Growth inhibition of murine neuroblastoma cells by c-myc with cell cycle arrest in G2/M.
c-myc and N-myc belong to the myc family of proteins that plays an important role in cell proliferation, differentiation and apoptosis. The N-myc gene is amplified in aggressive neuroblastoma and c-myc is overexpressed in many lymphomas and cancers. However, c-myc has not been implied in tumorigenesis or progression of neuroblastoma. We therefore investigated the so far unknown effects of c-myc overexpression on the aggressiveness of neuroblastoma cells with single copy N-myc. c-myc overexpression in serum-deprived murine NXS2 neuroblastoma cells led to cell cycle progression and massive apoptosis, causing a net decrease of viable cells. In serum-replete medium c-myc caused NXS2 cells to arrest in G2/M. Furthermore, c-myc decreased clonogenic growth of neuroblastoma cells. Taken together, these data suggest that c-myc attenuates the malignant phenotype of NXS2 neuroblastoma cells. Thus, although c-myc increased NXS2 tumor mass in vivo, c-myc appears to have decreased malignant potency in neuroblastoma cells compared to N-myc. This may be one reason why c-myc does not play a role in neuroblastomagenesis.
Ushmorov
Alexey
A
University Children's Hospital, Ulm, Germany.
Debatin
Klaus-Michael
KM
Beltinger
Christian
C
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002455:Cell Division; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D005260:Female; D016195:G2 Phase; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D009447:Neuroblastoma / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D016271:Proto-Oncogene Proteins c-myc