AUGMENTATION OF METALLOPROTEINASE (GELATINASE) ACTIVITY SECRETED FROMROUS-SARCOMA VIRUS-INFECTED CELLS CORRELATES WITH TRANSFORMING ACTIVITY OF SRC

To search for the biochemical properties of cells relevant to transfor mation by p60(v-src), we examined the activities and amounts of metall oproteinase (gelatinase) released from chicken embryonic fibroblasts i nfected with various mutants of Rous sarcoma virus by zymography and i mmunoblotting, While nontransforming Src proteins, including cellular p60(c-src) and its nonmyristylated form, had no stimulatory effect, wi ld-type p60(v-src) and the transforming mutant of cellular p60(c-src) stimulated the secretion and proteolytic activation of metalloproteina ses, Moreover, the activation of metalloproteinase secretion strongly correlated with the invasiveness of cells assayed by the modified Boyd en Chamber method, Chimeric mutants between v-src and c-src, which are transforming but produce less distinct morphological changes in infec ted cells, also stimulated the secretion of metalloproteinases as well as wild-type p60(v-src). Deletion mutants of v-Src in which varying p ortions of the NH2-terminal half of p60(v-src) are deleted stimulated secretion to a level similar to that of wild-type regardless of the de gree of morphological change they induce, Together with Src protein, o ther oncogene products including Yes, Fps, ErbB and Crk were also foun d to stimulate the secretion of metalloproteinases, Thus, these result s suggest that transformation of cells with src and other oncogenes is closely secretion of metalloproteinases associated with the enhanced that may play an important role in tumor invasion and metastasis.