METASTASIS-ASSOCIATED MTS1 AND NM23 GENES AFFECT TUBULIN POLYMERIZATION IN B16 MELANOMAS - A POSSIBLE MECHANISM OF THEIR REGULATION OF METASTATIC BEHAVIOR OF TUMORS

The nm23 and mts1 genes are associated with the expression of the meta static phenotype. We have shown previously that modulation of metastat ic behaviour produces parallel changes in the expression of these gene s and that the expression of the two genes is co-regulated. Here we sh ow that modulation of gene expression affects the process of tubulin p olymerisation. B16 melanoma cell lines F1 and ML8 were treated with al pha melanocyte stimulating hormone (MSH) and all-trans. retinoic acid (RA) respectively. MSH reduced the proportion of nm23 + and increased mts1 + F1 cells, with a 55 % decrease in the ratio nm23:mts1. In paral lel, MSH increased the expression of depolymerised form of tubulin in these cells. Treatment of ML8 cells with RA decreased mts1 positivity to a greater extent that nm23 positivity and the nm23:mts1 ratio incre ased by 70% and, in parallel, reduced the expression of depolymerised form of tubulin. These data suggest that nm23 and mts1 gene expression regulates the biological behaviour of the tumour cell and confer on i t invasive and metastasizing properties by affecting the state of tubu lin polymerisation.