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 alpha2, alpha3 and
beta1 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
beta1 integrin subunit protein and significant alteration in cell morphology - these cell lines resemble N-myc-over-expressing
neuroblastoma cells. In addition to reduced beta1 subunit levels, the
osteosarcoma-derived N-myc transfectants exhibit little or no
alpha3beta1 integrin complexes, either intracellular or at the cell surface. Finally, reduced amounts of
alpha3 integrin subunit in these cell lines occur at the level of
alpha3 integrin mRNA, although post-transcriptional mechanisms may also be involved, particularly with inability of pre-beta1
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.