DJ-1, a novel regulator of the tumor suppressor PTEN

Raymond H. Kim, Malte Peters, Yingju Jang, Wei Shi, Melania Pintilie, Graham C. Fletcher, Carmela DeLuca, Jennifer Liepa, Lily Zhou, Bryan Snow, Richard C. Binari, Armen S. Manoukian, Mark R. Bray, Fei Fei Liu, Ming Sound Tsao, Tak W. Mak

Research output: Contribution to journalArticle

420 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)263-273
Number of pages11
JournalCancer Cell
Volume7
Issue number3
DOIs
StatePublished - Mar 2005

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    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. https://doi.org/10.1016/j.ccr.2005.02.010