N-MYC OVER-EXPRESSION DOWN-REGULATES ALPHA-3-BETA-1 INTEGRIN EXPRESSION IN HUMAN SAOS-2 OSTEOSARCOMA CELLS

Alterations in adhesion to the extracellular matrix mediated by integr in receptors are commonly observed in a wide variety of transformed/tu mor classes, Reductions in the expression of several integrin subunits have been documented in human neuroblastoma cell lines that over-expr ess the neuroblastoma-associated oncogene N-myc. Neuroblastoma cells t ransfected with a cDNA encoding N-myc on a high-expression plasmid exh ibit greatly reduced levels of alpha 2, alpha 3 and beta 1 integrin su bunits, with concomitant rounding of cells on substrata, In the curren t studies, we examined whether integrin downregulation by N-myc is cel l-type specific by transfecting a human N-myc cDNA into Saos-2 human o steosarcoma cells and evaluating integrin expression, Several N-myc-ex pressing cell lines were isolated which exhibit reduced levels of beta 1 integrin subunit protein and significant alteration in cell morphol ogy - these cell lines resemble N-myc-over-expressing neuroblastoma ce lls, In addition to reduced beta 1 subunit levels, the osteosarcoma-de rived, N-myc transfectants exhibit little or no alpha 3 beta 1 integri n complexes, either intracellular or at the cell surface, Finally, red uced amounts of alpha 3 integrin subunit in these cell lines occur at the level of alpha 3 integrin mRNA, although post-transcriptional mech anisms may also be involved, particularly with inability of pre-beta 1 protein to mature, These results confirm our previous studies demonst rating integrin downregulation by an N-myc-dependent process and, in a ddition, demonstrate lack of cell-type specificity in the action of N- myc on integrin extracellular matrix receptor expression when comparin g neural precursor (neuroblastoma) cells with connective tissue (osteo sarcoma) cells.