INDUCTION OF CARCINOMA CELL-MIGRATION ON VITRONECTIN BY NF-KAPPA-B-DEPENDENT GENE-EXPRESSION

Integrin alpha v beta 5 promotes FG carcinoma cell adhesion to vitrone ctin yet requires protein kinase C (PKC) activation for migration on t his ligand. Here we report that this PKC-dependent cell motility event requires NF-kappa B-dependent transcription. Specifically, a componen t within nuclear extracts prepared from PKC-stimulated FG cells exhibi ted a significant increase in binding activity to a synthetic oligonuc leotide containing a consensus kappa B sequence. These nuclear DNA-bin ding complexes were shown to be comprised of p65 and p50 NF-kappa B/re l family members and appeared functionally active because they promote d transcription of a reporter construct containing a kappa B site. The NF-kappa B activation event was directly linked to the alpha v beta 5 motility response because the NF-kappa B-binding oligonucleotide, whe n introduced into FG cells, inhibited cell migration on vitronectin bu t not on collagen and had no effect on cell. adhesion to either ligand . These results suggest that the detected DNA-binding complexes intera ct with kappa B transcriptional elements to regulate gene expression r equired for alpha v beta 5-dependent cell motility on vitronectin.