Overexpression of the Parkinson Disease Protein DJ-1 and its Regulator PTEN in Gestational Trophoblastic Disease

Abstract

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.