Molecular mechanism of transcriptional activation of human gelatinase B by proximal promoter.

Gelatinase B is a regulated matrix metalloproteinase with important role in the remodeling of extracellular matrix and many pathological conditions such as tumor invasion and rheumatoid arthritis, physiological processes including embryonic growth and development, migration of blood leukocytes into tissues and tissue remodeling. Elevated levels of certain MMPs are believed to be associated with various pathological states. We cloned the 5'-flanking 600 bp sequence of human gelatinase B gene by PCR, which controls the expression of the gene by ligating it to the chloramphenicol acetyltransferase gene. Four kinds of cell lines were used to transiently transfect. Deletion analysis revealed that 100 bp (-600 to -500 bp) contributed positively to induction by tumour necrosis factor. The 100 bp contains NF-kappa B site, Ap-1 site, PEA3 and Sp-1 site. The expression of the human gelatinase B gene varied in different cells in the presence of TNF.NF-kappa B factor may play an important role in regulating the gene expression. Comparison of the finding with those for the promoter of gelatinase A, collagenase and stromelysin shows that the determinant for the inducibility of the gelatinase B gene is more complex.