title: DJ-1, a novel regulator of the tumor suppressor PTEN.
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.
authors.affiliation: Advanced Medical Discovery Institute, The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Toronto, Canada M5G 2C1.
authors.forename: Raymond H
authors.initials: RH
authors.lastname: Kim
authors.forename: Malte
authors.initials: M
authors.lastname: Peters
authors.forename: YingJu
authors.initials: Y
authors.lastname: Jang
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Melania
authors.initials: M
authors.lastname: Pintilie
authors.forename: Graham C
authors.initials: GC
authors.lastname: Fletcher
authors.forename: Carmela
authors.initials: C
authors.lastname: DeLuca
authors.forename: Jennifer
authors.initials: J
authors.lastname: Liepa
authors.forename: Lily
authors.initials: L
authors.lastname: Zhou
authors.forename: Bryan
authors.initials: B
authors.lastname: Snow
authors.forename: Richard C
authors.initials: RC
authors.lastname: Binari
authors.forename: Armen S
authors.initials: AS
authors.lastname: Manoukian
authors.forename: Mark R
authors.initials: MR
authors.lastname: Bray
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Liu
authors.forename: Ming-Sound
authors.initials: MS
authors.lastname: Tsao
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016923:Cell Death; D002460:Cell Line; D018450:Disease Progression; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000502:physiology; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017956:Photoreceptor Cells, Invertebrate / Q000002:abnormalities / Q000378:metabolism / Q000648:ultrastructure; D000071617:Protein Deglycase DJ-1; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000502:physiology
chemical_list: D014408:Biomarkers, Tumor; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D010744:Phosphoric Monoester Hydrolases; D000071617:Protein Deglycase DJ-1; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C494918:AKT1 protein, human; C494917:Akt1 protein, Drosophila; C105131:PARK7 protein, human; C487101:PTEN protein, Drosophila