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 integrin 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 experiments were performed in which an N-myc cDNA (on the episomal expression vector pREP4; high-level constitutive expression is driven by an RSV-LTR promoter) was introduced into SKNSH cells. Expression of N-myc produced significant morphological alterations in transfected cells; one subpopulation of cells remained spread on tissue culture substrata, while a second subpopulation became rounded and grew as multi-cellular aggregates. Spread (attached) cells expressed low levels of N-myc and high levels of beta 1 integrin, while rounded (loose) cells expressed relatively high levels of N-myc and low levels of beta 1 integrin. Maintenance of transfected cells in higher concentrations of selective agent produced a higher proportion of loose cells, which expressed even greater 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 for cell:extracellular cellular matrix interaction and possibly cell:cell adhesion.
Case Western Reserve University, School of Medicine, Department of Molecular Biology and Microbiology, Cleveland, OH 44106, USA.
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D000818:Animals; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006801:Humans; D019012:Integrin beta1 / Q000032:analysis*; D051379:Mice; D019006:Neural Cell Adhesion Molecules / Q000032:analysis; D009447:Neuroblastoma / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
D019012:Integrin beta1; D019006:Neural Cell Adhesion Molecules