Human stromelysin gene promoter activity is modulated by transcription factor ZBP-89

Matrix metalloproteinase expression is under strict regulation in physiolog ical conditions, Disruption of the regulatory mechanisms can lead to tissue destruction and is associated with tumour invasion and metastasis. Using t he one-hybrid assay technique with a cis-element in the promoter region of the stromelysin (matrix metalloproteinase-3) gene, a cDNA encoding a transc ription factor termed ZBP-89 was obtained. The interaction between ZBP-89 a nd the stromelysin promoter element was confirmed by electrophoretic mobili ty shift assays with a recombinant ZBP-89. Reporter gene expression under t he control of the stromelysin promoter in transiently transfected cells was significantly increased when the cells were cotransfected with a ZBP-89 ex pression construct, These results indicate that ZBP-89 interacts with the s tromelysin promoter and upregulates its activity. As ZBP-89 expression is k nown to be increased in gastric carcinoma cells, induction of stromelysin e xpression may be a significant factor in tumour metastasis. (C) 1999 Federa tion of European Biochemical Societies.