INDUCTION OF 18A2 MTS1 GENE-EXPRESSION AND ITS EFFECTS ON METASTASIS AND CELL-CYCLE CONTROL/

The metastasis associated 18A2/mts1 gene was inserted into the mammali an expression vector pMAMneo placing it under the control of the dexam ethasone-inducible MMTV promoter. The construct was transfected into d examethasone receptor negative F1 and receptor positive F10 cells of t he B16 murine melanoma. The transferred gene was switched on in two tr ansfectant clones of F10, by exposure to 10(-6) M dexamethasone, but n ot in clones of the receptor negative F1 line. One of the F10 transfec tant clones (F10-192/10) was characterized further. A 13.5-fold increa se in 18A2/mts1 transcripts was found in this clone upon exposure to d examethasone. There was also a seven-fold increase in lung colonizatio n in an experimental metastasis assay, together with increased express ion of depolymerized tubulin and enhanced detection of p53 protein. Th e number of cells in the S phase increased by 2.5-fold following dexam ethasone treatment of the clone. These data suggest a direct involveme nt of the 18A2/mts1 gene in lung colonization by the tumor cells. The 18A2/mts1 protein promotes tubulin depolymerization, sequesters the p5 3 phosphoprotein, and induces the cells to enter the S phase, but the relevance of these in the metastatic process remains to be elucidated.