Augmentation of metalloproteinase (gelatinase) activity secreted from Rous sarcoma virus-infected cells correlates with transforming activity of src.
To search for the biochemical properties of cells relevant to transformation by p60v-src, we examined the activities and amounts of metalloproteinase (gelatinase) released from chicken embryonic fibroblasts infected with various mutants of Rous sarcoma virus by zymography and immunoblotting. While nontransforming Src proteins, including cellular p60c-src and its nonmyristylated form, had no stimulatory effect, wild-type p60v-src and the transforming mutant of cellular p60c-src stimulated the secretion and proteolytic activation of metalloproteinases. Moreover, the activation of metalloproteinase secretion strongly correlated with the invasiveness of cells assayed by the modified Boyden Chamber method. Chimeric mutants between v-src and c-src, which are transforming but produce less distinct morphological changes in infected cells, also stimulated the secretion of metalloproteinases as well as wild-type p60v-src. Deletion mutants of v-Src in which varying portions of the NH2-terminal half of p60v-src are deleted stimulated secretion to a level similar to that of wild-type regardless of the degree of morphological change they induce. Together with Src protein, other oncogene products including Yes, Fps, ErbB and Crk were also found to stimulate the secretion of metalloproteinases. Thus, these results suggest that transformation of cells with src and other oncogenes is closely associated with the enhanced secretion of metalloproteinases that may play an important role in tumor invasion and metastasis.
Hamaguchi
M
M
Department of Molecular Pathogenesis, Nagoya University School of Medicine, Japan.
Yamagata
S
S
Thant
A A
AA
Xiao
H
H
Iwata
H
H
Mazaki
T
T
Hanafusa
H
H
D000818:Animals; D001358:Avian Sarcoma Viruses; D002472:Cell Transformation, Viral / Q000235:genetics; D002642:Chick Embryo; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism / Q000821:virology; D018093:Gelatinases / Q000378:metabolism*; D006868:Hydrolysis; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000378:metabolism*; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics*; D019716:Tissue Inhibitor of Metalloproteinase-2
D011506:Proteins; D019716:Tissue Inhibitor of Metalloproteinase-2; D015688:Oncogene Protein pp60(v-src); D016392:Proto-Oncogene Proteins pp60(c-src); D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2