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

Matrix metalloproteinase expression is under strict regulation in physiological conditions. Disruption of the regulatory mechanisms can lead to tissue destruction and is associated with tumour invasion and metastasis. Using the one-hybrid assay technique with a cis-element in the promoter region of the stromelysin (matrix metalloproteinase-3) gene, a cDNA encoding a transcription factor termed ZBP-89 was obtained. The interaction between ZBP-89 and the stromelysin promoter element was confirmed by electrophoretic mobility shift assays with a recombinant ZBP-89. Reporter gene expression under the control of the stromelysin promoter in transiently transfected cells was significantly increased when the cells were cotransfected with a ZBP-89 expression construct. These results indicate that ZBP-89 interacts with the stromelysin promoter and upregulates its activity. As ZBP-89 expression is known to be increased in gastric carcinoma cells, induction of stromelysin expression may be a significant factor in tumour metastasis.