TRANSFECTION OF HUMAN NM23-H1 INTO THE HUMAN MDA-MB-435 BREAST-CARCINOMA CELL-LINE - EFFECTS ON TUMOR METASTATIC POTENTIAL, COLONIZATION AND ENZYMATIC-ACTIVITY

We report the phenotypic effects of transfection of human nm23-H1 cDNA into the human MDA-MB-435 breast carcinoma cell line. Upon mammary fa t pad or subcutaneous injection into nude mice, both the nm23-H1 and c ontrol transfected lines produced primary tumors; however, the nm23-H1 -transfected lines produced metastases in significantly fewer mice tha n did control transfected lines. Reductions in tumor metastatic potent ial in vivo were accompanied by decreased colonization in soft agar an d an altered colonization response to transforming growth factor beta in vitro. Total nucleoside diphosphate kinase activity, an enzymatic a ctivity possessed by the Nm23 family, was not directly correlated with Nm23-H1 expression levels or suppression of metastatic potential in a ll cases examined. The data establish that nm23-H1 has functional supp ressive effects on the tumor metastatic potential of a human breast ca rcinoma cell line, and suggest that it may regulate signal responsiven ess in the colonization response.