Role of a Novel Antioncogene that Prevents Metastatic Spread of Disease

The aim of this project is to determine the role of a novel antioncogene (nm23) in the spread of cancer. We propose that nm23 prevents metastatic spread of disease by down regulation of proteolytic activity that is necessary for tumor cells to migrate to other parts of the body. We have developed two methods for measurement of nm23 in tumor cells and they are comparable. We have set up test for the cathepsin D and the other components of the urokinase plasminogen activator system. We have measured the expression of these components in 3 cell lines, 8 primary cultures grown in nude mice and more than 50 human primary breast tumors. The relationships of these proteolytic components and nm23 expression are in progress. We have prepared a new selection vector containing the nm23 gene and have transfected one cell line. Nm23 expression in these transfected cells ranges from 3 to over 50-fold when compared to the non-transfected cells. These cells are presently being analyzed to define affects of over expression of nm23 and relationship to perturbations of proteolytic factors.