Author/Authors :
Kim، نويسنده , , Raymond H. and Peters، نويسنده , , Malte and Jang، نويسنده , , YingJu and Shi، نويسنده , , Wei and Pintilie، نويسنده , , Melania and Fletcher، نويسنده , , Graham C. and DeLuca، نويسنده , , Carmela and Liepa، نويسنده , , Jennifer and Zhou، نويسنده , , Lily and Snow، نويسنده , , Bryan and Binari، نويسنده , , Richard C. and Manoukian، نويسنده , , Armen S. and Bray، نويسنده , , Mark R. and Liu، نويسنده , , Fei-Fei and Tsao، نويسنده , , Ming-Sound and Mak، نويسنده , , Tak W.، نويسنده ,
Abstract :
Summary
osphatidylinositol 3′ kinase (PI3′K) pathway, which regulates cell survival, is antagonized by the PTEN tumor suppressor. The regulation of PTEN is unclear. A genetic screen of Drosophila gain-of-function mutants identified DJ-1 as a suppressor of PTEN function. In mammalian cells, DJ-1 underexpression results in decreased phosphorylation of PKB/Akt, while DJ-1 overexpression leads to hyperphosphorylation of PKB/Akt and increased cell survival. In primary breast cancer samples, DJ-1 expression correlates negatively with PTEN immunoreactivity and positively with PKB/Akt hyperphosphorylation. In 19/23 primary non-small cell lung carcinoma samples, DJ-1 expression was increased compared to paired nonneoplastic lung tissue, and correlated positively with relapse incidence. DJ-1 is thus a key negative regulator of PTEN that may be a useful prognostic marker for cancer.
