OVER-EXPRESSION OF TRANSFECTED N-MYC ONCOGENE IN HUMAN SKNSH NEUROBLASTOMA-CELLS DOWN-REGULATES EXPRESSION OF BETA-1 INTEGRIN SUBUNIT

Amplification of the N-myc oncogene is associated with progression of neuroblastoma in humans, Previous studies indicated that neuroblastoma cell lines which are amplified for the N-myc gene and over-express N- myc exhibit enhanced tumorigenic properties when injected into athymic nude mice, In addition, neuroblastoma cells which over-express N-myc (IMR32 cells) expressed little or no beta 1, alpha 2, or alpha 3 integ rin subunits, as compared with cells which do not express N-myc (SKNSH cells), In order to probe the possible relationship between N-myc and beta 1 integrin gene expressions more directly, transfection experime nts were performed in which an N-myc cDNA (on the episomal expression vector pREP4; high-level constitutive expression is driven by an RSV-L TR promoter) was introduced into SKNSH cells, Expression of N-myc prod uced significant morphological alterations in transfected cells; one s ubpopulation of cells remained spread on tissue culture substrata, whi le a second subpopulation became rounded and grew as multi-cellular ag gregates, Spread (attached) cells expressed low levels of N-myc and hi gh levels of beta 1 integrin, while rounded (loose) cells expressed re latively high levels of N-myc and low levels of beta 1 integrin, Maint enance of transfected cells in higher concentrations of selective agen t produced a higher proportion of loose cells, which expressed even gr eater amounts of N-myc and even less beta 1 integrin; a similar effect was observed in attached cells, Interestingly, loose cell populations expressed elevated levels of the neural cell adhesion molecule [NCAM] . The results presented here infer that N-myc regulates the expression of the beta 1 integrin and NCAM cell-surface receptors responsible fo r cell:extracellular matrix interaction and possibly cell:cell adhesio n.