RELATIONSHIP OF NM23 TO PROTEOLYTIC FACTORS, PROLIFERATION AND MOTILITY IN BREAST-CANCER TISSUES AND CELL-LINES

Low expression of the antimetastatic gene nm23 has been associated wit h shorter overall survival in breast cancer. To better understand the mechanism(s) of action of this protein, we compared the levels of the nm23 protein in 152 breast cancer samples with other factors known to be involved in metastasis or related to prognosis. There was no signif icant relationship between either of the nm23 isoforms and cathepsin D (Cat-D), urokinase plasminogen activator (uPA), its inhibitor (PAI-I) , steroid hormone receptors or ploidy status. A marginal inverse corre lation was observed between per cent S-phase and nm23-H1 expression (r = - 0.193, P= 0.047) and a positive correlation was observed between u PA receptor (uPAR) and both nm23-H1 (r= 0.263, P= 0.0018) and nm23-H2 (r= 0.230, P= 0.0064). The nm23-H1 gene was transfected into MDA-MB-23 1 human breast cancer cells and 12 clones were selected, of which two were characterized extensively. We found no significant differences in Cat-D, uPA, PAI-1 or uPAR, as a function of nm23 expression in either the MDA-MB-231 cells or the transfected clones. Compared with the par ent cell line, we did observe a dose-dependent decrease in growth fact or-stimulated motility and a decrease in metastatic potential in two c lones with four- and eightfold elevated nm23-H1 expression, whereas th e proliferative activities were similar. We conclude that the decrease d metastatic potential might be related to down-regulation of growth f actor-stimulated motility.