Gene expression profiling reveals differentially expressed genes in ovarian cancer of the hen: support for oviductal origin?

Gene expression profiling reveals differentially expressed genes in ovarian cancer of the hen: support for oviductal origin?
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基因表达谱揭示了母鸡卵巢癌中差异表达的基因:支持输卵管起源?

DOI:
10.1007/s12672-010-0024-8
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发表时间:
2010
期刊:
影响因子:
3
通讯作者:
Johnson,PatriciaAnn
Johnson,PatriciaAnn
中科院分区:
医学2区
文献类型:
--
作者:
Treviño,LindseyS;Giles,JamesR;Wang,Wei;Urick,MaryEllen;Johnson,PatriciaAnn

文献摘要

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卵巢癌的死亡率很高,部分原因是缺乏早期发现和对疾病起源的不完全了解。母鸡是卵巢癌的唯一自发模型,因此可以帮助识别和测试早期检测策略和治疗方法。我们的目的是联合收割机和微阵列技术相结合,以确定差异表达的基因在正常母鸡卵巢组织与卵巢癌母鸡。我们发现,在鸡卵巢肿瘤中表达上调的转录本富含输卵管相关基因。定量实时PCR和免疫组化证实了输卵管相关基因在正常输卵管和卵巢中的表达,从母鸡早期和晚期卵巢肿瘤,但不是在正常卵巢表面上皮。此外,在我们的分析中鉴定的输卵管相关基因之一,配对盒2与人类卵巢癌有关,并可能作为该疾病的标志物。此外,雌激素受体1 mRNA在早期肿瘤中过度表达,表明输卵管相关基因的表达可能受雌激素调节。我们还鉴定了编码分泌蛋白的输卵管相关基因,这些分泌蛋白可能代表假定的血清生物标志物。输卵管相关基因在早期肿瘤中的表达与人类卵巢癌相似,肿瘤类似于正常的苗勒管上皮。这些数据表明,鸡卵巢肿瘤可能产生于替代网站,包括输卵管。
Ovarian cancer has a high mortality rate due, in part, to the lack of early detection and incomplete understanding of the origin of the disease. The hen is the only spontaneous model of ovarian cancer and can therefore aid in the identification and testing of early detection strategies and therapeutics. Our aim was to combine the use of the hen animal model and microarray technology to identify differentially expressed genes in ovarian tissue from normal hens compared with hens with ovarian cancer. We found that the transcripts up-regulated in chicken ovarian tumors were enriched for oviduct-related genes. Quantitative real-time PCR and immunohistochemistry confirmed expression of oviduct-related genes in normal oviduct and in ovaries from hens with early- and late-stage ovarian tumors, but not in normal ovarian surface epithelium. In addition, one of the oviduct-related genes identified in our analysis, paired box 2 has been implicated in human ovarian cancer and may serve as a marker of the disease. Furthermore, estrogen receptor 1 mRNA is over-expressed in early-stage tumors, suggesting that expression of the oviduct-related genes may be regulated by estrogen. We have also identified oviduct-related genes that encode secreted proteins that could represent putative serum biomarkers. The expression of oviduct-related genes in early-stage tumors is similar to what is seen in human ovarian cancer, with tumors resembling normal Müllerian epithelium. These data suggest that chicken ovarian tumors may arise from alternative sites, including the oviduct.