Reduction of Ha-ras-induced cellular transformation by elevated expressionof protein phosphatase type 2A

The role of serine/threonine protein phosphatase type ZA (PP2A) in cellular growth control has not yet been thoroughly established. Earlier experiment s with okadaic acid, a phosphatase inhibitor, suggested that PP2A may act a s an anti-oncogene, although a direct role for this enzyme in the transform ation process has not been demonstrated. We therefore investigated whether altered levels of PP2A expression would affect the transformation of mouse fibroblasts by the Ha-ras oncogene. Here we report that cells with elevated levels of PP2A expression were more resistant to focus formation induced b y Ha-ras. At the molecular level, this was paralleled by the reduced Ha-ras -stimulated expression of the c-fos promoter, a proto-oncogene target for H a-ras signaling. Thus, our results support a negative role for PP2A in the process of cellular transformation and may ascribe tumor-suppressing functi ons to this enzyme. (C) 1999 Wiley-Liss, Inc.