生物谷報(bào)道：本月位于萊斯布里奇大學(xué)的科研人員以大鼠為模型利用microRNA表達(dá)譜分析、表觀基因組學(xué)以及蛋白組學(xué)方法對(duì)乳腺癌的發(fā)病表征進(jìn)行了最新闡釋（O. Kovalchuk, etal. Estrogen-Induced Rat Breast Carcinogenesis is Characterized by Alterations in DNA Methylation, Histone Modifications and Aberrant MicroRNA Expression. Cell Cycle 6:16, 2010-2018）,。
此項(xiàng)研究的最大成果是首次論證了乳腺組織中miRNA的表達(dá)與DNA甲基化和組蛋白甲基化形態(tài)變化中表現(xiàn)出的表觀遺傳失調(diào)密切相關(guān),。特別是使用miRNA微陣列（由LC Sciences提供）對(duì)E2誘導(dǎo)產(chǎn)生的大鼠癌癥發(fā)生過(guò)程進(jìn)行分析，發(fā)現(xiàn)miR-22,，miR-99a,，miR-99b以及miR-127出現(xiàn)下調(diào)，并且顯示這些下調(diào)的miRNAs與目標(biāo)致癌基因的活動(dòng)加劇有關(guān),。通過(guò)一系列深入的研究,，研究人員得出以下結(jié)論：DNA以及組蛋白的甲基化變化，更為重要的是,，miRNA組的異?？赡軙?huì)導(dǎo)致出現(xiàn)具有腫瘤特異性表型的表觀遺傳基因程序重組細(xì)胞，而這些細(xì)胞日后將引起惡性轉(zhuǎn)化,。
Abstract
Breast cancer is the most common malignancy in women continuing to rise worldwide. Breast cancer emerges through a multi‑step process, encompassing progressive changes from a normal cell to hyperplasia (with and without atypia), carcinoma in situ, invasive carcinoma, and metastasis. In the current study, we analyzed the morphological changes and alterations of DNA methylation, histone methylation and microRNA expression during estradiol‑17b (E2)‑induced mammary carcinogenesis in female August Copenhagen Irish (ACI) rats. E2‑induced breast carcinogenesis in ACI rats provides a physiologically relevant and genetically defined animal model for studying human sporadic breast cancer. The pattern of morphological changes in mammary glands during E2‑induced carcinogenesis was characterized by transition from normal appearing alveolar and ductular hyperplasia to focal hyperplastic areas of atypical glands and ducts accompanied by a rapid and sustained loss of global DNA methylation, LINE‑1 hypomethylation, loss of histone H3 lysine 9 and histone H4 lysine 20 trimethylation, and altered microRNAs expression. More importantly, these alterations in the mammary tissue occurred after six weeks of E2‑treatment, whereas the atypical hyperplasia, which represents a putative precursor lesion to mammary carcinoma in this model, was detected only after twelve weeks of exposure, demonstrating clearly that these events are directly associated with the effects of E2 and are not a consequence of the preexisting preneoplastic lesions. The results of this study show that deregulation of cellular epigenetic processes plays a crucial role in the mechanism of E2‑induced mammary carcinogenesis in ACI rats, especially in the tumor initiation process.
全文下載：
Estrogen-Induced Rat Breast Carcinogenesis is Characterized by Alterations in DNA Methylation, Histone Modifications and Aberrant MicroRNA Expression.
本文由LC Sciences中國(guó)分公司杭州聯(lián)川生物提供
