CHARACTERIZATION OF 2 SPLICE VARIANTS OF METASTASIS-ASSOCIATED HUMAN MTS1 GENE

The mts1 gene is one of the genes specifically expressed in mouse metastatic tumors and tumor cell lines. In this paper, we present data on cloning and sequencing of two variants of human mts1 cDNAs (hu-mts1 and hu-mts1 (var)), as well as of the corresponding region in the human genome. Comparison of the genomic sequence with the sequence of the mts1 cDNAs demonstrates presence of two alternatively spliced variants of the mts1 in the human osteosarcoma cell line (OHS). The alternative splicing occurs within the 5'-untranslated region (UTR) of human mts1 pre-mRNA. Both splice variants, hu-mts1 and hu-mts1 (var), retain similar stability in the cells, contain one open reading frame coding for the MTS1 protein and differ only slightly in their translational capacity. The splice variants demonstrate dramatic variations in the level of expression in different human tissues and in human tumor cell lines. Although we have not revealed substantial differences in the mode of action of the two splice variants in the cells, the observed tissue specificity of expression supports the notion that it plays an important role in determining the activity of mts1 in different tissues.