Expression and clinical role of DJ-1, a negative regulator of PTEN, in ovarian carcinoma.
The aim of this study was to analyze the expression and clinical role of DJ-1, a negative regulator of PTEN (phosphatase and tensin homolog deleted on chromosome 10), in ovarian carcinoma, and investigate the putative association between DJ-1 levels and expression of its transcriptional regulators specificity protein 1 (Sp1) and specificity protein 3 (Sp3). Effusions (n = 72) and solid tumors (n = 57, 42 primary and 15 metastases) were analyzed for DJ-1 messenger RNA (mRNA) expression using reverse transcriptase-polymerase chain reaction. Most specimens (48 effusions, 50 solid tumors) were additionally analyzed for Sp1 and Sp3 mRNA expression. PTEN protein expression was analyzed in 201 effusions and 92 solid tumors using immunohistochemistry. DJ-1 mRNA was expressed in more than 80% of specimens, with no preferential anatomical site. DJ-1 expression was positively associated with Sp1 expression in effusions (P = .03) and with Sp1 (P = .02) and Sp3 (P = .002) expression in solid tumors. In effusions, DJ-1 expression was higher in postchemotherapy compared with prechemotherapy specimens (P = .012). Higher DJ-1 levels (P = .027) and more advanced FIGO stage (IV versus III; P = .003) correlated with shorter progression-free survival in univariate analysis for patients with postchemotherapy effusions. PTEN expression was low in effusions and solid tumors (23% and 13%, respectively), and its expression showed no association with DJ-1 levels or survival. Our data show that DJ-1 is frequently expressed in advanced-stage ovarian carcinoma at all anatomical sites and is coexpressed with its transcriptional regulators Sp1 and Sp3. In contrast, PTEN expression is infrequent in this disease. These findings may provide one of the molecular mechanisms that mediate cancer cell survival and aggressiveness in this tumor.
Davidson
Ben
B
Pathology Clinic, Rikshospitalet-Radiumhospitalet Medical Center, Montebello, N-0310 Oslo, Norway. bend@ulrik.uio.no
Hadar
Rivka
R
Schlossberg
Anat
A
Sternlicht
Tamar
T
Slipicevic
Ana
A
Skrede
Martina
M
Risberg
Björn
B
Flørenes
Vivi Ann
VA
Kopolovic
Juri
J
Reich
Reuven
R
D000328:Adult; D000368:Aged; D001202:Ascitic Fluid / Q000737:chemistry; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged; D015513:Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D010051:Ovarian Neoplasms; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D016066:Pleural Effusion, Malignant / Q000737:chemistry; D000071617:Protein Deglycase DJ-1; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016329:Sp1 Transcription Factor / Q000378:metabolism; D051705:Sp3 Transcription Factor / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; C497121:SP3 protein, human; D016329:Sp1 Transcription Factor; D051705:Sp3 Transcription Factor; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human