N-myc expression switched off and class I human leukocyte antigen expression switched on after somatic cell fusion of neuroblastoma cells.
Neuroblastomas often show amplification and high expression of the N-myc oncogene. N-myc expression could be explained as a consequence of gene amplification, but an alternative possibility is that expression primarily results from the inactivation or loss of some factor that normally represses the N-myc gene. To test this idea, we fused N-myc-overexpressing neuroblastoma cell lines with lines that do not express N-myc. In the resulting hybrids, N-myc expression turned out to be switched off, although amplified N-myc copies were still present. This suggests that N-myc overexpression in neuroblastomas results, at least in part, from the inactivation of a suppressor gene that is present in normal cells. In rat neuroblastomas, it has been found that N-myc can switch off class I major histocompatibility complex (MHC) expression. Therefore, we analyzed in our hybrid cells whether suppression of N-myc results in reexpression of human class I MHC genes. Because this was found to be the case, the picture emerges of a hierarchic pathway that connects a putative tumor-suppressor gene with the expression of N-myc and consequently of class I MHC, thus affecting the potential immunogenic properties of neuroblastomas.
Department of Clinical Oncology, University Hospital Leiden, The Netherlands.
R
R
Versteeg
C
C
van der Minne
A
A
Plomp
A
A
Sijts
A
A
van Leeuwen
P
P
Schrier
D000818:Animals; D015152:Blotting, Northern; D006224:Cricetinae; D015972:Gene Expression Regulation, Neoplastic; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D006822:Hybrid Cells; D007739:L Cells; D051379:Mice; D009447:Neuroblastoma / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D014407:Tumor Cells, Cultured
D006680:HLA Antigens; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc