Tumor suppressor gene regulation of an inhibitor of angiogenesis.

摘要

Tumor suppressor genes are active in normal cells but their activity is lost as a cell progresses towards malignancy. In baby hamster kidney (BK) cells, a tumor suppressor gene regulates growth in part by controlling the elaboration of a matrix glycoprotein able to inhibit neovascularization in vivo. Biochemical, immunological and functional assays have been used to identity this inhibitory protein as a 140 kDa proteolytic isoform of the platelet and matrix glycoprotein, thrombospondin-1(TSP1). Normal, non-angiogenic BHK cells containing an active tumor suppressor gene make and secrete 4.2-8.6 fold more gp140 protein than transformed, angiogenic cells lacking this tumor suppressor gene. Regulation of gp140/TSP is at the RNA level. When BHK cells containing a temperature sensitive tumor suppressor gene were grown at 38