ERα-CITED1 co-regulated genes expressed during pubertal mammary gland development:: implications for breast cancer prognosis
ERα-CITED1 co-regulated genes expressed during pubertal mammary gland development:: implications for breast cancer prognosis
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DOI：
10.1038/sj.onc.1210468
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发表时间：
2007-09-27
期刊：
影响因子：
8
通讯作者：
Martin, F.
中科院分区：
文献类型：
--
作者：
McBryan, J.;Howlin, J.;Martin, F.
表达微阵列分析确定了超过930个基因在青春期调节小鼠乳腺。最突出的是基因的表达增加与青春期发育平行，并保持高此后。Wnt、转化生长因子β和雌激素信号通路的成员明显过多。与CITED 1基因敲除小鼠的表达数据比较，发现了一个雌激素应答基因亚组，在CITED 1缺失的情况下显示出表达改变。包括在该子集中的是斯钙素2（Stc 2）和双调蛋白（Areg）。染色质免疫沉淀显示，ER α结合雌激素反应元件在Stc 2和Areg基因在青春期的乳腺。此外，CITED 1和ER α定位于青春期乳腺的相同上皮细胞，支持这两种蛋白质在正常发育期间相互作用的作用。在人类乳腺癌数据集中，Stc 2、Areg和CITED 1的表达与ER α的表达平行。与ER α相似，CITED 1表达与乳腺癌的良好预后相关，这意味着在乳腺肿瘤中ER α-CITED 1共调节信号通路的潜在维持可以指示良好的预后。
Expression microarray analysis identified over 930 genes regulated during puberty in the mouse mammary gland. Most prominent were genes whose expression increased in parallel with pubertal development and remained high thereafter. Members of the Wnt, transforming growth factor-beta and oestrogen-signalling pathways were significantly overrepresented. Comparison to expression data from CITED1 knockout mice identified a subset of oestrogen-responsive genes displaying altered expression in the absence of CITED1. Included in this subset are stanniocalcin2 (Stc2) and amphiregulin (Areg). Chromatin immunoprecipitation revealed that ER alpha binds to oestrogen response elements in both the Stc2 and Areg genes in the mammary gland during puberty. Additionally, CITED1 and ER alpha localize to the same epithelial cells of the pubertal mammary gland, supporting a role for interaction of these two proteins during normal development. In a human breast cancer data set, expression of Stc2, Areg and CITED1 parallel that of ER alpha. Similar to ERa, CITED1 expression correlates with good outcome in breast cancer, implying that potential maintenance of the ER alpha-CITED1 co-regulated signalling pathwayin breast tumours can indicate good prognosis.