HEAT-SHOCK MODULATES THE EXPRESSION OF THE METASTASIS-ASSOCIATED GENEMTS1 AND PROLIFERATION OF MURINE AND HUMAN CANCER-CELLS

Mts1 is a metastasis-associated gene of the S-100 gene family and code s for a Ca2+-binding protein. It is highly expressed in murine and hum an cancers of high invasive and metastatic potential. Recent work has shown that the mts1 protein might be involved in cell cycle regulation . An upregulation of its expression drives cells into the S phase, tog ether with an enhanced expression of p53 phosphoprotein, which has led to the suggestion that mts1 protein might be sequestering p53 thereby abrogating the G(1)-S checkpoint control normally exerted by p53. Pre liminary studies showed that expression of mts1 is downregulated by hy perthermia. We present evidence that in murine BL6 melanoma cells and human HUT cells that hyperthermia downregulates the mts1 gene. It is a lso downregulated in heat-resistant variants of the B16 melanoma and H UT cells. In parallel, there is a decrease in the size of the S phase fraction and an increase in the doubling time of cells. Cell subjected to hyperthermia show an 2- to 3.5-fold increase in the expression of HSP28 which has been shown to possess a proliferation inhibitory actio n. It is postulated that a complete regulatory loop involving mts1, p5 3, and HSP28 might be involved in cell proliferation.