Transformation of epithelial Madin-Darby canine kidney cells with p60(v-src) induces expression of membrane-type 1 matrix metalloproteinase and invasiveness.
Membrane-type 1 matrix metalloproteinase (MT1-MMP) is expressed both in carcinoma cells and in surrounding stromal fibroblasts. MT1-MMP localizes to the surface of tumor cells and is thought to play an important role in tumor invasion. To analyze the mechanism of MT1-MMP gene expression in epithelial tumor cells, the dog kidney epithelial cell line Madin-Darby canine kidney (MDCK) was transformed by oncogenes, including v-src, and expression of MT1-MMP was examined. Transformation of MDCK cells with v-src resulted in loss of cell-to-cell contacts and morphological change. Expression of MT1-MMP in v-src-transformed cells was identified by Northern and Western blotting. Gelatin zymography analysis showed that progelatinase A in the culture medium was processed from latent to activated form by MDCK cells transformed with v-src. The MDCK cells transformed by v-src were tumorigenic in the subcutis (ectopic) and kidney (orthotopic) of nude mice and spontaneously metastasized to the lung after orthotopic implantation. These results suggest that MT1-MMP induced by v-src transformation may promote invasiveness of transformed cells.
Kadono
Y
Y
Department of Molecular Virology and Oncology, Cancer Research Institute, School of Medicine, Kanazawa University, Ishikawa, Japan.
Okada
Y
Y
Namiki
M
M
Seiki
M
M
Sato
H
H
D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004285:Dogs; D004790:Enzyme Induction; D004847:Epithelial Cells / Q000473:pathology; D053511:Matrix Metalloproteinase 14; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000096:biosynthesis* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics*; D014162:Transfection
C507096:Mmp14 protein, mouse; D009363:Neoplasm Proteins; D015688:Oncogene Protein pp60(v-src); D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D053511:Matrix Metalloproteinase 14