Alterations in adhesion to the extracellular matrix mediated by integrin receptors are commonly observed in a wide variety of transformed/tumor classes. Reductions in the expression of several integrin subunits have been documented in human neuroblastoma cell lines that over-express the neuroblastoma-associated oncogene N-myc. Neuroblastoma cells transfected with a cDNA encoding N-myc on a high-expression plasmid exhibit greatly reduced levels of a2, a3 and b1 integrin subunits with concomitant rounding of cells on substrata. In the current studies, we examined whether integrin downregulation by N-myc is cell-type specific by transfecting a human N-myc cDNA into Saos-2 human osteosarcoma cells and evaluating integrin expression. Several N-myc-expressing cell lines were isolated which exhibit reduced levels of b1 integrin subunit protein and significant alteration in cell morphology - these cell lines resemble N-myc-over-expressing neuroblastoma cells. In addition to reduced b1 subunit levels, the osteosarcoma-derived N-myc transfectants exhibit little or no a3b1 integrin complexes, either intracellular or at the cell surface. Finally, reduced amounts of a3 integrin subunit in these cell lines occur at the level of a3 integrin mRNA, although post-transcriptional mechanisms may also be involved, particularly with inability of pre-b1 protein to mature. These results confirm our previous studies demonstrating integrin downregulation by an N-myc-dependent process and, in addition, demonstrate lack of cell-type specificity in the action of N-myc on integrin extracellular matrix receptor expression when comparing neural precursor (neuroblastoma) cells with connective tissue (osteosarcoma) cells.