Interaction in vivo and in vitro of the metastasis-inducing S100 protein, S100A4 (p9Ka) with S100A1

The calcium-binding protein S100A4 (p9Ka) has been shown to cause a metasta tic phenotype in rodent mammary tumor cells and in transgenic mouse model s ystems. mRNA for S100A4 (p9Ka) is present at a generally higher level in br east carcinoma than in benign breast tumor specimens, and the presence of i mmunocytochemically detected S100A4 correlates strongly with a poor prognos is for breast cancer patients. Recombinant S100A4 (p9Ka) has been reported to interact in vitro with cytoskeletal components and to form oligomers, pa rticularly homodimers in vitro, Using the yeast two-hybrid system, a strong interaction between S100A4 (p9Ka) and another S100 protein, S100A1, was de tected. Site-directed mutagenesis of conserved amino acid residues involved in the dimerization of S100 proteins abolished the interactions. The inter action between S100A4 and S100A1 was also observed in vitro using affinity column chromatography and gel overlay techniques. Both S100A1 and S100A4 ca n. occur in the same cultured mammary cells, suggesting that in cells conta ining both proteins, S100A1 might modulate the metastasis-inducing capabili ty of S100A4.