Open AccessN-myc expression switched off and class I human leukocyte antigen expression switched on after somatic cell fusion of neuroblastoma cells.
Author(s) -
Rogier Versteeg,
Caroline van der Minne,
A Plomp,
Alice J.A.M. Sijts,
A van Leeuwen,
Peter I. Schrier
Publication year - 1990
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.10.10.5416
Subject(s) - biology , n myc , neuroblastoma , major histocompatibility complex , gene , cancer research , gene expression , microbiology and biotechnology , oncogene , mhc class i , fusion gene , suppressor , ectopic expression , cell culture , genetics , cell cycle , ganglioneuroma
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.