首页> 外文期刊>Virus Research: An International Journal of Molecular and Cellular Virology >Gene expression array analyses predict increased proto-oncogene expression in MMTV induced mammary tumors.
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Gene expression array analyses predict increased proto-oncogene expression in MMTV induced mammary tumors.

机译:基因表达阵列分析预测在MMTV诱导的乳腺肿瘤中原癌基因表达增加。

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摘要

Exogenous infection by milk-borne mouse mammary tumor viruses (MMTV) typically induce mouse mammary tumors in genetically susceptible mice at a rate of 90-95% by 1 year of age. In contrast to other transforming retroviruses, MMTV acts as an insertional mutagen and under the influence of steroid hormones induces oncogenic transformation after insertion into the host genome. As these events correspond with increases in adjacent proto-oncogene transcription, we used expression array profiling to determine which commonly associated MMTV insertion site proto-oncogenes were transcriptionally active in MMTV induced mouse mammary tumors. To verify our gene expression array results we developed real-time quantitative RT-PCR assays for the common MMTV insertion site genes found in RIII/Sa mice (int-1/wnt-1, int-2/fgf-3, int-3/Notch 4, and fgf8/AIGF) as well as two genes that were consistently up regulated (CCND1, and MAT-8) and two genes that were consistently down regulated (FN1 and MAT-8) in the MMTV induced tumors as compared to normal mammary gland. Finally, each tumor was also examined histopathologically. Our expression array findings support a model whereby just one or a few common MMTV insertions into the host genome sets up a dominant cascade of events that leave a characteristic molecular signature.
机译:牛奶传播的小鼠乳腺肿瘤病毒(MMTV)的外源感染通常在1岁时以90-95%的比例在遗传易感小鼠中诱发小鼠乳腺肿瘤。与其他转化逆转录病毒相反,MMTV充当插入诱变剂,在类固醇激素的影响下,插入宿主基因组后可诱导致癌性转化。由于这些事件与相邻原癌基因转录的增加相对应,因此我们使用表达阵列分析来确定哪些通常相关的MMTV插入位点原癌基因在MMTV诱导的小鼠乳腺肿瘤中具有转录活性。为了验证我们的基因表达阵列结果,我们针对在RIII / Sa小鼠中发现的常见MMTV插入位点基因(int-1 / wnt-1,int-2 / fgf-3,int-3)开发了实时定量RT-PCR分析/ Notch 4和fgf8 / AIGF),以及与MMTV诱导的肿瘤相比,两个一直被上调的基因(CCND1和MAT-8)和两个一直被下调的基因(FN1和MAT-8)。正常的乳腺。最后,还对每个肿瘤进行了组织病理学检查。我们的表达阵列发现支持了一种模型,在该模型中,仅一个或几个常见的MMTV插入宿主基因组就建立起主要事件级联,从而留下了特征性的分子特征。

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