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.

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
  • Phosphatidylinositol 3-Kinases
  • 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