Caspase activity is downregulated in choriocarcinoma: a cDNA array differential expression study
Caspase activity is downregulated in choriocarcinoma: a cDNA array differential expression study
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DOI：
10.1136/jcp.2005.028027
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发表时间：
2006-02-01
影响因子：
3.4
通讯作者：
Cheung, ANY
中科院分区：
文献类型：
--
作者：
Fong, PY;Xue, WC;Cheung, ANY
背景资料：胎盘滋养细胞是一种假恶性组织，其发病机制尚不清楚，目的：探讨Caspase 8和Caspase 10在滋养细胞肿瘤发生中的作用。方法：cDNA阵列杂交技术用于比较绒毛膜癌细胞系中基因表达谱（Escherichia coli，JEG，and BeWo）和正常妊娠早期人胎盘，然后用定量真实的时间聚合酶链反应和免疫组织化学进行确认。结果：Atlas（TM）human cDNA表达芯片和Atlas（TM）human 1.2芯片均检测到绒毛膜癌中caspase 10表达下调。与正常胎盘相比，葡萄胎（p = 0.035）和绒毛膜癌（p = 0.002）中Caspase 10 mRNA的表达显著降低。Caspase 8和Caspase 10蛋白主要表达于细胞滋养细胞和合体滋养细胞，在绒毛膜癌中的表达明显低于其他滋养细胞组织（p < 0.05）。caspase 8和10的免疫反应性与先前通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记评估的凋亡指数相关（p = 0.02和p = 0.04）和M30（分别为p < 0.001和p = 0.003）方法。这些结果提示，衣壳蛋白酶8和10的下调可能参与了绒毛膜癌的发病机制。
Background: Placental trophoblast can be considered to be pseudomalignant tissue and the pathogenesis of gestational trophoblastic diseases remains to be clarified.Aims: To examine the role of caspases 8 and 10, identified by differential expression, on trophoblast tumorigenesis.Methods: 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.Results: Downregulation of caspase 10 in choriocarcinoma was detected by both Atlas (TM) human cDNA expression array and Atlas (TM) 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.Conclusions: These results suggest that the downregulation of capases 8 and 10 might contribute to the pathogenesis of choriocarcinoma.