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Characterization of the homeodomain gene emx2: sequence conservation, expression analysis, and a search for mutations in endometrial cancers.

机译:同源域基因emx2的表征:序列保守,表达分析和寻找子宫内膜癌的突变。

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摘要

Previous loss-of-heterozygosity studies in endometrial carcinoma mapped a putative tumor suppressor gene to 10q25.3-26.1. An analysis of genomic sequences for the deletion interval showed several expressed sequence tags and the homeodomain gene EMX2, a homologue of Drosophila melanogaster empty spiracles. Expression studies showed that EMX2 transcripts are abundant in the adult uterus and that message levels seem to be inversely correlated with endometrial proliferation. EMX2 RNA was more abundant in quiescent postmenopausal endometrium than in premenopausal endometrium. We found decreased EMX2 expression in a subset of primary endometrial tumors, and four of six endometrial cancer cell lines investigated failed to express EMX2. The predicted protein showed extensive amino acid conservation with EMX2 sequences from several vertebrates. There was also considerable evolutionary conservation in the 3' untranslated region. To examine the potential function of EMX2 in endometrial tumorigenesis, we investigated 20 primary tumors and 6 endometrial cancer cell lines for mutations. Two primary tumors had mutations. Inactivation or reduced expression of EMX2 in cancers, coupled with increased expression in the quiescent endometrium, indicate that this homeodomain gene is involved in maintenance of the differentiated state.
机译:先前在子宫内膜癌中进行的杂合性丧失研究将推定的抑癌基因定位于10q25.3-26.1。对缺失间隔的基因组序列的分析显示了几个表达的序列标签和同源结构域基因EMX2,果蝇黑空果的同源物。表达研究表明,成人子宫中EMX2转录本丰富,信息水平似乎与子宫内膜增生呈负相关。绝经后子宫内膜中的EMX2 RNA比绝经前子宫内膜中的丰富。我们发现在原发性子宫内膜肿瘤的一个子集中EMX2表达下降,并且研究的六个子宫内膜癌细胞系中有四个未能表达EMX2。预测的蛋白质显示出来自多个脊椎动物的EMX2序列具有广泛的氨基酸保守性。在3'非翻译区中也有相当大的进化保守性。为了检查EMX2在子宫内膜肿瘤发生中的潜在功能,我们调查了20个原发肿瘤和6个子宫内膜癌细胞系中的突变。两个原发性肿瘤具有突变。 EMX2在癌症中的失活或表达降低,以及在子宫内膜的表达增加,表明该同源结构域基因参与了分化状态的维持。

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