Protein kinase C-independent expression of stromelysin by platelet-derived growth factor, ras oncogene, and phosphatidylcholine-hydrolyzing phospholipase C.
Changes in the expression of several genes play critical roles in cell growth and tumor transformation. A number of proteases are increased in some tumors, and the level of these enzymes correlates with the metastatic potential of several cancer cell lines. Stromelysin, with the widest substrate specificity, can degrade the extracellular matrix conferring metastatic potential to tumor cells. The mechanisms whereby growth factors and oncogenes control the expression of stromelysin are beginning to be characterized. In the study shown here we also identify a region in the stromelysin promoter which is involved in the induction of stromelysin in response to platelet-derived growth factor, phosphatidylcholine-hydrolyzing phospholipase C, and ras oncogene. Our results are consistent with the notion that platelet-derived growth factor/phosphatidylcholine-hydrolyzing phospholipase C induces stromelysin gene expression through a phorbol myristate acetate/protein kinase C-independent mechanism by acting through elements in the stromelysin promoter distinct from the 12-O-tetradecanoylphorbol-13-acetate-responsive element.
Diaz-Meco
M T
MT
Medicina y Cirugía Experimental, Hospital General Gregorio Maranón, Madrid, Spain.
Quiñones
S
S
Municio
M M
MM
Sanz
L
L
Bernal
D
D
Cabrero
E
E
Saus
J
J
Moscat
J
J
D001483:Base Sequence; D015152:Blotting, Northern; D002478:Cells, Cultured; D002872:Chromosome Deletion; D005786:Gene Expression Regulation / Q000187:drug effects; D011905:Genes, ras / Q000187:drug effects; D006801:Humans; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000235:genetics*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010957:Plasmids; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D015183:Restriction Mapping; D013696:Temperature; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000235:genetics*
D009838:Oligodeoxyribonucleotides; D010982:Platelet-Derived Growth Factor; D012313:RNA; D011493:Protein Kinase C; D010738:Type C Phospholipases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D013755:Tetradecanoylphorbol Acetate