Kim, R.H., Peters, M., Jang, Y., Shi, W., Pintilie, M., Fletcher, G.C., DeLuca, C., Liepa, J., Zhou, L., Snow, B., Binari, R.C., Manoukian, A.S., Bray, M.R., Liu, F.F., Tsao, M.S., Mak, T.W. (2005). DJ-1, a novel regulator of the tumor suppressor PTEN.  Cancer Cell 7(3): 263--273.

FBrf0183770

Research paper

The phosphatidylinositol 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.