Repression of thrombospondin-1 expression, a natural inhibitor of angiogenesis, in polyoma middle T transformed NIH3T3 cells.

Thrombospondin-1 (TSI) is a modular extracellular matrix glycoprotein and expressed by many cell types in culture. Thrombospondin-1 inhibits angiogenesis and its expression inversely correlates with the degree of invasiveness and metastasis in tumor cell lines. Here, we demonstrate that expression of Polyoma middle T oncogene in NIH3T3 cells results not only in transformation but also represses expression of three thrombospondin isoforms, TS1, TS2, and TS3. Similar results were observed in ras, and to a lesser extent in src transformed NIH3T3 cells. Middle T and ras transformed cells expressed higher levels of c-jun mRNA, while the src transformed cells expressed higher levels of junB mRNA when compared to control cells. Thus, repression of thrombospondin levels appears to play an important role in establishment and maintenance of a malignant phenotype. This is mediated, at least in part, by alteration in c-jun activity in middle T and ras transformed NIH3T3 cells.