Drosophila tumor suppressor PTEN controls cell size and number by antagonizing the Chico/PI3-kinase signaling pathway

The human tumor suppressor gene PTEN encodes a putative cytoskeleton-associ ated molecule with both protein phosphatase and phosphatidylinositol 3,4,5- trisphosphate (PIP3) 3-phosphatase activities. In cell culture, the lipid p hosphatase activity of this protein is involved in regulating cell prolifer ation and survival but the mechanism by which PTEN inhibits tumorigenesis i n vivo is not fully established. Here we show that the highly evolutionaril y conserved Drosophila PTEN homolog, DPTEN, suppresses hyperplastic growth in flies by reducing cell size and number. We demonstrate that DPTEN modula tes tissue mass by acting antagonistically to the Drosophila Class I phosph atidylinositol 3-kinase, Dp110, and its upstream activator Chico, an insuli n receptor substrate homolog. Surprisingly, although DPTEN does not general ly affect cell fate determination, it does appear to regulate the subcellul ar organization of the actin cytoskeleton in multiple cell types. From thes e data, we propose that DPTEN has a complex role in regulating tissue and b ody size. It acts in opposition to Dp110 to control cell number and growth, while coordinately influencing events at the cell periphery via its effect s on the actin cytoskeleton.