DJ-1, a novel regulator of the tumor suppressor PTEN.
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.
Kim
Raymond H
RH
Advanced Medical Discovery Institute, The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Toronto, Canada M5G 2C1.
Peters
Malte
M
Jang
YingJu
Y
Shi
Wei
W
Pintilie
Melania
M
Fletcher
Graham C
GC
DeLuca
Carmela
C
Liepa
Jennifer
J
Zhou
Lily
L
Snow
Bryan
B
Binari
Richard C
RC
Manoukian
Armen S
AS
Bray
Mark R
MR
Liu
Fei-Fei
FF
Tsao
Ming-Sound
MS
Mak
Tak W
TW
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
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