Fong P-Y, Xue W-C, Ngan H Y S, Chiu P-M, Chan K Y K, Tsao S W, Cheung A N Y
Department of Pathology, University of Hong Kong, Pokfulam, Queen Mary Hospital, Hong Kong, China.
J Clin Pathol. 2006 Feb;59(2):179-83. doi: 10.1136/jcp.2005.028027.
Placental trophoblast can be considered to be pseudomalignant tissue and the pathogenesis of gestational trophoblastic diseases remains to be clarified.
To examine the role of caspases 8 and 10, identified by differential expression, on trophoblast tumorigenesis.
cDNA array hybridisation was used to compare gene expression profiles in choriocarcinoma cell lines (JAR, JEG, and BeWo) and normal first trimester human placentas, followed by confirmation with quantitative real time polymerase chain reaction and immunohistochemistry. Caspase 10 and its closely related family member caspase 8 were analysed.
Downregulation of caspase 10 in choriocarcinoma was detected by both Atlastrade mark human cDNA expression array and Atlastrade mark human 1.2 array. Caspase 10 mRNA expression was significantly lower in hydatidiform mole (p = 0.035) and chorioarcinoma (p = 0.002) compared with normal placenta. The caspase 8 and 10 proteins were expressed predominantly in the cytotrophoblast and syncytiotrophoblast, respectively, with significantly lower expression in choriocarcinomas than other trophoblastic tissues (p < 0.05). Immunoreactivity for both caspase 8 and 10 correlated with the apoptotic index previously assessed by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (p = 0.02 and p = 0.04, respectively) and M30 (p < 0.001 and p = 0.003, respectively) approaches.
These results suggest that the downregulation of capases 8 and 10 might contribute to the pathogenesis of choriocarcinoma.
胎盘滋养层可被视为假恶性组织，妊娠滋养层疾病的发病机制仍有待阐明。
研究通过差异表达鉴定出的半胱天冬酶8和10在滋养层肿瘤发生中的作用。
采用cDNA阵列杂交技术比较绒毛膜癌细胞系（JAR、JEG和BeWo）与正常孕早期人胎盘的基因表达谱，随后通过定量实时聚合酶链反应和免疫组织化学进行验证。分析了半胱天冬酶10及其密切相关的家族成员半胱天冬酶8。
通过Atlastrade标记的人cDNA表达阵列和Atlastrade标记的人1.2阵列均检测到绒毛膜癌中半胱天冬酶10的下调。与正常胎盘相比，葡萄胎（p = 0.035）和绒毛膜癌（p = 0.002）中半胱天冬酶10 mRNA表达显著降低。半胱天冬酶8和10蛋白分别主要在细胞滋养层和合体滋养层表达，在绒毛膜癌中的表达明显低于其他滋养层组织（p < 0.05）。半胱天冬酶8和10的免疫反应性分别与先前通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法（分别为p = 0.02和p = 0.04）和M30法（分别为p < 0.001和p = 0.003）评估的凋亡指数相关。
这些结果表明半胱天冬酶8和10的下调可能有助于绒毛膜癌的发病机制。
