Epigenetic silencing of DSC3 is a common event in human breast cancer.
Epigenetic silencing of DSC3 is a common event in human breast cancer.
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DOI：
10.1186/bcr1273
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Futscher BW
中科院分区：
文献类型：
--
作者：
Oshiro MM;Kim CJ;Wozniak RJ;Junk DJ;Muñoz-Rodríguez JL;Burr JA;Fitzgerald M;Pawar SC;Cress AE;Domann FE;Futscher BW
桥粒桥粒蛋白3(Desmocolin 3，DSC3)是钙离子依赖的细胞黏附分子超家族中的一员，也是桥粒的主要成分。桥粒蛋白如DSC3对维持组织结构是不可或缺的，这些成分的丢失会导致缺乏黏附和获得细胞的流动性。DSC3在乳腺癌细胞系和原发乳腺肿瘤中表达下调；然而，DSC3的缺失不是由于基因缺失或基因的大体重排。在这项研究中，我们研究了DSC3基因在原发乳腺肿瘤标本中表达的表观遗传沉默的流行率。我们用亚硫酸氢盐基因组测序方法分析了32例乳腺癌组织中DSC3基因启动子区域的甲基化状态。我们还使用了实时定量RT-PCR方法，分析了所有乳腺肿瘤标本中DSC3的表达。最后，除了亚硫酸氢盐测序和RT-PCR外，我们还使用体内核酸酶可及性分析来确定DSC3阴性乳腺癌细胞系CpG岛区的染色质结构。在32例乳腺癌中，有23例(72%)DSC3表达下调，包括：22例浸润性导管癌、7例浸润性小叶癌、2例转移至淋巴结的浸润性导管癌和1例粘液导管癌。在23例DSC3表达缺失的标本中，13例(56%)与启动子区胞嘧啶高甲基化有关。此外，DSC3的表达仅限于上皮来源的细胞，其mRNA和蛋白的表达在高比例的乳腺肿瘤细胞系中缺失(79%)。最后，DSC3启动子的DNA高甲基化与一个封闭的染色质结构高度相关。这些结果表明，DSC3的表达缺失在乳腺肿瘤标本中是一种常见的事件，并且DSC3基因沉默在乳腺肿瘤中经常与胞嘧啶甲基化和伴随的染色质结构的改变有关。
Desmocollin 3 (DSC3) is a member of the cadherin superfamily of calcium-dependent cell adhesion molecules and a principle component of desmosomes. Desmosomal proteins such as DSC3 are integral to the maintenance of tissue architecture and the loss of these components leads to a lack of adhesion and a gain of cellular mobility. DSC3 expression is down-regulated in breast cancer cell lines and primary breast tumors; however, the loss of DSC3 is not due to gene deletion or gross rearrangement of the gene. In this study, we examined the prevalence of epigenetic silencing of DSC3 gene expression in primary breast tumor specimens. We used bisulfite genomic sequencing to analyze the methylation state of the DSC3 promoter region from 32 primary breast tumor specimens. We also used a quantitative real-time RT-PCR approach, and analyzed all breast tumor specimens for DSC3 expression. Finally, in addition to bisulfite sequencing and RT-PCR, we used an in vivo nuclease accessibility assay to determine the chromatin architecture of the CpG island region from DSC3-negative breast cancer cells lines. DSC3 expression was downregulated in 23 of 32 (72%) breast cancer specimens comprising: 22 invasive ductal carcinomas, 7 invasive lobular breast carcinomas, 2 invasive ductal carcinomas that metastasized to the lymph node, and a mucoid ductal carcinoma. Of the 23 specimens showing a loss of DSC3 expression, 13 (56%) were associated with cytosine hypermethylation of the promoter region. Furthermore, DSC3 expression is limited to cells of epithelial origin and its expression of mRNA and protein is lost in a high proportion of breast tumor cell lines (79%). Lastly, DNA hypermethylation of the DSC3 promoter is highly correlated with a closed chromatin structure. These results indicate that the loss of DSC3 expression is a common event in primary breast tumor specimens, and that DSC3 gene silencing in breast tumors is frequently linked to aberrant cytosine methylation and concomitant changes in chromatin structure.
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影响因子：
30.8
作者：
Futscher, BW;Oshiro, MM;Domann, FE
通讯作者：
Domann, FE
DOI：
10.1186/bcr651
发表时间：
2003
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Kowalski PJ;Rubin MA;Kleer CG
通讯作者：
Kleer CG
影响因子：
8
作者：
Costa, FF;Verbisck, NV;Camargo, AA
通讯作者：
Camargo, AA
影响因子：
3.5
作者：
Johnson, GK;Organ, CC
通讯作者：
Organ, CC
影响因子：
8
作者：
Millar, DS;Ow, KK;Clark, SJ
通讯作者：
Clark, SJ