Role of ERRF, a novel ER-related nuclear factor, in the growth control of ER-positive human breast cancer cells.
Role of ERRF, a novel ER-related nuclear factor, in the growth control of ER-positive human breast cancer cells.
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DOI：
10.1016/j.ajpath.2011.11.025
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发表时间：
2012-03
期刊：
影响因子：
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通讯作者：
Dan Su;Xiaoying Fu;S. Fan;Xiao Wu;Xin-xin Wang;Liya Fu;Xueyuan Dong;J. Ni;Li Fu;Zhengmao Zhu;Jin-Tang Dong
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文献类型：
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作者：
Dan Su;Xiaoying Fu;S. Fan;Xiao Wu;Xin-xin Wang;Liya Fu;Xueyuan Dong;J. Ni;Li Fu;Zhengmao Zhu;Jin-Tang Dong
雌激素-雌激素受体α (ER)信号在乳腺癌的生长过程中起着重要作用，同时也是正常乳腺上皮细胞分化的必要条件。然而，这种功能转换是如何发生的仍然未知。基于一项确定了几个乳腺癌基因突变的全基因组测序研究，我们检查了一些基因的突变、表达水平以及对细胞增殖和肿瘤发生的功能影响。我们提供了31个细胞系和367个原发性乳腺癌肿瘤的C1orf64或er相关因子（ERRF）的数据。虽然ERRF突变并不常见（79例中有1例或1.3%），但其在乳腺癌中的表达上调，且在低期肿瘤中表达上调更为常见。此外，ERRF表达的增加与ER和/或孕激素受体（PR）阳性显著相关，这在人表皮生长因子受体2 （HER2）阴性肿瘤中仍然有效。在er阳性肿瘤中，ERRF表达与HER2状态呈负相关。此外，较高的ERRF蛋白表达与更好的无病生存期和总生存期显著相关，特别是在ER和/或pr阳性和her2阴性肿瘤（腔内A亚型）中。从功能上讲，在两种er阳性乳腺癌细胞系T-47D和MDA-MB-361中，敲低ERRF可以抑制细胞的体外生长和异种移植模型中的肿瘤发生。这些结果表明，ERRF在雌激素er介导的乳腺癌细胞生长中起作用，因此可能是一个潜在的治疗靶点。
Whereas estrogen–estrogen receptor α (ER) signaling plays an important role in breast cancer growth, it is also necessary for the differentiation of normal breast epithelial cells. How this functional conversion occurs, however, remains unknown. Based on a genome-wide sequencing study that identified mutations in several breast cancer genes, we examined some of the genes for mutations, expression levels, and functional effects on cell proliferation and tumorigenesis. We present the data for C1orf64 or ER-related factor (ERRF) from 31 cell lines and 367 primary breast cancer tumors. Whereas mutation of ERRF was infrequent (1 of 79 or 1.3%), its expression was up-regulated in breast cancer, and the up-regulation was more common in lower-stage tumors. In addition, increased ERRF expression was significantly associated with ER and/or progesterone receptor (PR) positivity, which was still valid in human epidermal growth factor receptor 2 (HER2)–negative tumors. In ER-positive tumors, ERRF expression was inversely correlated with HER2 status. Furthermore, higher ERRF protein expression was significantly associated with better disease-free survival and overall survival, particularly in ER- and/or PR-positive and HER2-negative tumors (luminal A subtype). Functionally, knockdown of ERRF in two ER-positive breast cancer cell lines, T-47D and MDA-MB-361, suppressed cell growthin vitroand tumorigenesis in xenograft models. These results suggest that ERRF plays a role in estrogen-ER–mediated growth of breast cancer cells and could, thus, be a potential therapeutic target.