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 metastatic phenotype in rodent mammary tumor cells and in transgenic mouse model systems. mRNA for S100A4 (p9Ka) is present at a generally higher level in breast carcinoma than in benign breast tumor specimens, and the presence of immunocytochemically detected S100A4 correlates strongly with a poor prognosis for breast cancer patients. Recombinant S100A4 (p9Ka) has been reported to interact in vitro with cytoskeletal components and to form oligomers, particularly homodimers in vitro. Using the yeast two-hybrid system, a strong interaction between S100A4 (p9Ka) and another S100 protein, S100A1, was detected. Site-directed mutagenesis of conserved amino acid residues involved in the dimerization of S100 proteins abolished the interactions. The interaction between S100A4 and S100A1 was also observed in vitro using affinity column chromatography and gel overlay techniques. Both S100A1 and S100A4 can occur in the same cultured mammary cells, suggesting that in cells containing both proteins, S100A1 might modulate the metastasis-inducing capability of S100A4.
Wang
G
G
Cancer and Polio Research Fund Laboratories, School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, United Kingdom.
Rudland
P S
PS
White
M R
MR
Barraclough
R
R
D000818:Animals; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000737:chemistry*; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D017354:Point Mutation; D051381:Rats; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000032:analysis / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000737:chemistry; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D002135:Calcium-Binding Proteins; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C110294:S100A1 protein; C470944:S100a4 protein, mouse; C499412:S100a4 protein, rat; C077591:S100A4 protein, human