Department of Pathology, Queen Mary Hospital, the University of Hong Kong, Pokfulam Road, Hong Kong, China.
Int J Gynecol Pathol. 2010 Sep;29(5):468-75. doi: 10.1097/PGP.0b013e3181de3068.
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.
DJ-1 被发现通过调节氧化损伤和细胞凋亡在人类神经退行性疾病和癌症中起重要作用。DJ-1 也是癌症中经常发生突变的肿瘤抑制基因 PTEN 的调节剂。在这项研究中，我们研究了 DJ-1 和 PTEN 在正常胎盘和妊娠滋养细胞疾病中的表达与细胞凋亡指数和 p53 状态的关系。共检索了 95 个滋养层样本进行免疫组织化学研究，而 79 个滋养层样本、3 个正常胎盘和 2 个绒毛膜癌细胞系用于定量实时逆转录聚合酶链反应检测。在滋养层样本中，DJ-1 和 PTEN 免疫染色指数之间存在显著相关性（P=0.013）。完全性葡萄胎（P<0.01）和绒毛膜癌（P<0.01）中 DJ-1 和 PTEN 免疫反应性指数明显升高，与早期胎盘相比。定量实时逆转录聚合酶链反应还检测到葡萄胎（P<0.05）和绒毛膜癌（P<0.05）中 DJ-1 和 PTEN 的信使核糖核酸表达明显升高，与早期胎盘相比。DJ-1 与凋亡抵抗基因 Bcl-2 之间存在显著负相关（P=0.031），而 PTEN 与野生型 p53 之间存在显著正相关（P=0.019）。PTEN 还与胚胎干细胞转录因子 Stat3 和 Nanog 显示出显著相关性（P=0.001，0.015）。我们的研究结果首次表明，DJ-1 在妊娠滋养细胞疾病中同时在转录和蛋白水平上过度表达。过度表达的 DJ-1 可能在调节与 PTEN 和 p53 相关的滋养细胞凋亡活性中发挥作用。
