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

doi:10.1016/j.ccr.2005.02.010

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

Cancer Cell. 2005 Mar;7(3):263-73. doi: 10.1016/j.ccr.2005.02.010.

Authors

Raymond H Kim¹, 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

Affiliation

¹ Advanced Medical Discovery Institute, The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Toronto, Canada M5G 2C1.

PMID: 15766664
DOI: 10.1016/j.ccr.2005.02.010

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Genetically Modified
Biomarkers, Tumor
Breast Neoplasms / genetics
Breast Neoplasms / metabolism
Breast Neoplasms / pathology
Cell Death
Cell Line
Disease Progression
Drosophila Proteins / genetics
Drosophila Proteins / metabolism*
Drosophila melanogaster / physiology
Enzyme Activation
Female
Humans
Intracellular Signaling Peptides and Proteins
Lung Neoplasms / genetics
Lung Neoplasms / metabolism
Lung Neoplasms / pathology
Mice
Mice, Nude
Oncogene Proteins / genetics
Oncogene Proteins / metabolism*
PTEN Phosphohydrolase
Phosphatidylinositol 3-Kinases / metabolism*
Phosphoric Monoester Hydrolases / genetics
Phosphoric Monoester Hydrolases / metabolism*
Phosphorylation
Photoreceptor Cells, Invertebrate / abnormalities
Photoreceptor Cells, Invertebrate / metabolism
Photoreceptor Cells, Invertebrate / ultrastructure
Protein Deglycase DJ-1
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism*
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins / metabolism*
Proto-Oncogene Proteins c-akt
Signal Transduction / physiology

Substances

Biomarkers, Tumor
Drosophila Proteins
Intracellular Signaling Peptides and Proteins
Oncogene Proteins
Proto-Oncogene Proteins
AKT1 protein, human
Akt1 protein, Drosophila
Protein Serine-Threonine Kinases
Proto-Oncogene Proteins c-akt
PARK7 protein, human
Protein Deglycase DJ-1
Phosphoric Monoester Hydrolases
PTEN Phosphohydrolase
PTEN protein, Drosophila