Oncogene-mediated downregulation of RECK, a novel transformation suppressor gene

The RECK gene was initially isolated as a transformation suppressor gene en coding a novel membrane-anchored glycoprotein and later found to suppress t umor invasion and metastasis by regulating matrix metalloproteinase-9. Its expression is ubiquitous in normal tissues, but undetectable in many tumor cell lines and in fibroblastic lines transformed by various oncogenes. The RECK gene promoter has been cloned and characterized. One of the elements r esponsible for the oncogene-mediated downregulation of mouse RECK gene is t he Sp1 site, where the Sp1 and Sp3 factors bind. Sp1 transcription factor f amily is involved in the basal level of promoter activity of many genes, as well as in dynamic regulation of gene expression; in a majority of cases a s a positive regulator, or, as exemplified by the oncogene-mediated suppres sion of RECK gene expression, as a negative transcription regulator. The mo lecular mechanisms of the downregulation of mouse RECK gene and other tumor suppressor genes are just beginning to be uncovered. Understanding the reg ulation of these genes may help to develop strategies to restore their expr ession in tumor cells and, hence, suppress the cells' malignant behavior.