Expression of the Wnt antagonist DKK3 is frequently suppressed in sporadic epithelial ovarian cancer
Expression of the Wnt antagonist DKK3 is frequently suppressed in sporadic epithelial ovarian cancer
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DOI：
10.1007/s00432-010-0916-6
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发表时间：
2011-04-01
影响因子：
3.6
通讯作者：
An, Han-Xiang
中科院分区：
文献类型：
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作者：
You, An;Fokas, Emmanouil;An, Han-Xiang
Wnt信号通路在胚胎发育过程中起着重要作用，该通路的缺陷与肿瘤的发生有关。Dickkopf 3（DKK 3）是一种公认的Wnt信号传导抑制剂，在人类癌症中经常失活。然而，DKK 3在卵巢癌中的表达尚不清楚，我们利用数字差异显示技术研究了DKK 3在卵巢癌中的表达。实时荧光定量RT-PCR检测卵巢癌及正常卵巢组织中DKK 3 mRNA的表达。免疫组化法检测DKK 3蛋白在卵巢癌和正常卵巢组织中的表达情况，与CGAP中的正常卵巢组织和肿瘤组织相比，DKK 3蛋白的表达明显降低（P <0. 05）。与正常卵巢组织相比，63%（35/56）的卵巢肿瘤组织中DKK 3 mRNA表达降低（P < 0.02）。对13对配对的卵巢癌和邻近正常组织的分析显示，9对癌（69%）中DKK 3的转录显著下调（>两倍）。实时荧光定量PCR检测结果显示，66%（37/56）的卵巢癌中DKK 3蛋白表达缺失或弱表达，包括所有DKK 3基因转录水平低的肿瘤，这是首次发现DKK 3在卵巢癌中表达改变。后者可能是卵巢癌发生中Wnt通路激活的相关机制，但需要进一步研究来阐明DKK 3沉默在卵巢癌发生中的功能。
The Wnt pathway plays an important role in embryonic development, and defects in this pathway have been implicated in the tumorigenesis. The Dickkopf 3 (DKK3) is a putative Wnt signaling inhibitor that is frequently inactivated in human cancers. However, the expression of DKK3 in ovarian cancer remains unknown.We investigated the expression of DKK3 in silico using the Digital Differential Display. DKK3 mRNA expression was also analyzed by real-time RT-PCR in ovarian carcinomas and normal ovarian tissues. DKK3 protein expression was determined by immunohistochemistry in the same ovarian carcinomas and normal ovarian tissues.A significantly reduced expression of DKK3 (P < 0.05) was found after comparison of normal ovary- and tumor-derived libraries in the Cancer Genome Anatomy Project (CGAP). DKK3 mRNA expression was reduced in 63% (35 of 56) of tumors compared with normal ovarian samples (P < 0.02). Analysis of 13 matched pairs of ovarian carcinomas and adjacent normal tissues showed significant transcriptional downregulation of DKK3 (> twofold) in 9 paired carcinomas (69%). Loss or weak membranous expression of DKK3 protein was observed in 66% of ovarian cancers (37 of 56) including all tumors with low transcriptional level of DKK3 gene analyzed by real-time PCR.To our best knowledge, this is the first time to demonstrate altered expression of DKK3 in ovarian cancer. The latter could be a relevant mechanism for the activation of the Wnt pathway in the carcinogenesis of ovarian cancer but additional studies are required to elucidate the function of DKK3 silencing in ovarian carcinogenesis.