Reduction of Ha-ras-induced cellular transformation by elevated expression of protein phosphatase type 2A.
The role of serine/threonine protein phosphatase type 2A (PP2A) in cellular growth control has not yet been thoroughly established. Earlier experiments with okadaic acid, a phosphatase inhibitor, suggested that PP2A may act as an anti-oncogene, although a direct role for this enzyme in the transformation 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 by 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 Ha-ras signaling. Thus, our results support a negative role for PP2A in the process of cellular transformation and may ascribe tumor-suppressing functions to this enzyme.
D016475:3T3 Cells / Q000187:drug effects; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D003114:Colony-Forming Units Assay; D018076:DNA, Complementary / Q000235:genetics; D004790:Enzyme Induction; D016762:Genes, fos; D011905:Genes, ras; D051379:Mice; D019319:Okadaic Acid / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection