Overexpression of the Parkinson disease protein DJ-1 and its regulator PTEN in gestational trophoblastic disease.
DJ-1 is found to be important in human neurodegenerative diseases and cancers by regulating oxidative damage and apoptosis. DJ-1 is also a regulator of PTEN, a frequently mutated tumor suppressor gene in cancers. In this study, we investigated the expression of DJ-1 and PTEN in normal placentas and gestational trophoblastic disease in relation to apoptotic indices and p53 status. A total of 95 trophoblastic samples were retrieved for immunohistochemical study whereas 79 trophoblastic samples, 3 normal trophoblastic and 2 choriocarcinoma cell lines were collected for quantitative real time reverse transcription polymerase chain reaction detection. There was a significant correlation between DJ-1 and PTEN immunostaining indices in the trophoblastic samples (P=0.013). Significantly higher DJ-1 and PTEN immunoreactivity indices were found in the complete mole (P<0.01) and choricarcinoma (P<0.01) compared with the first trimester placenta. Quantitative real time reverse transcription polymerase chain reaction also detected significantly higher messenger ribonucleic acid expressions of DJ-1 and PTEN in hydatidiform moles (P<0.05) and choriocarcinomas (P<0.05) compared with the first trimester placentas. A significant negative correlation was found between DJ-1 and the apoptosis resistant gene Bcl-2 (P=0.031), whereas a positive correlation was shown between PTEN and wild-type p53 (P=0.019). Significant correlations between PTEN and embryonic stem cell transcription factors, Stat3 and Nanog, were also displayed (P=0.001, 0.015). Our findings showed, for the first time, overexpression of DJ-1 at both transcriptional and protein levels in gestational trophoblastic disease. Overexpressed DJ-1 may play a role in regulating apoptotic activities of trophoblasts in relation to PTEN and p53.
Zhang
Hui-Juan
HJ
Department of Pathology, Queen Mary Hospital, the University of Hong Kong, Pokfulam Road, Hong Kong, China.
Siu
Michelle Kwan-Yee
MK
Jiang
Li-Li
LL
Mak
Victor Chun-Yin
VC
Ngan
Hextan Yuen-Sheung
HY
Cheung
Annie Nga-Yin
AN
D017209:Apoptosis / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D031901:Gestational Trophoblastic Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis* / Q000235:genetics; D010920:Placenta / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D000071617:Protein Deglycase DJ-1; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014594:Uterine Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human