N-myc over-expression downregulates alpha 3 beta 1 integrin expression in human Saos-2 osteosarcoma cells

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 alpha 2, alpha 3 and beta 1 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 beta 1 integrin subunit protein and significant alteration in cell morphology - these cell lines resemble N-myc-over-expressing neuroblastoma cells, In addition to reduced beta 1 subunit levels, the osteosarcoma-derived, N-myc transfectants exhibit little or no alpha 3 beta 1 integrin complexes, either intracellular or at the cell surface, Finally, reduced amounts of alpha 3 integrin subunit in these cell lines occur at the level of alpha 3 integrin mRNA, although post-transcriptional mechanisms may also be involved, particularly with inability of pre-beta 1 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.