Role of ERRF, a Novel ER-Related Nuclear Factor, in the Growth Control of ER-Positive Human Breast Cancer Cells

被引:17
作者
Su, Dan [2 ]
Fu, Xiaoying [1 ]
Fan, Songqing [3 ]
Wu, Xiao [2 ]
Wang, Xin-Xin [4 ,5 ]
Fu, Liya [2 ]
Dong, Xue-Yuan [1 ]
Ni, Jianping Jenny [1 ]
Fu, Li [4 ,5 ]
Zhu, Zhengmao [2 ]
Dong, Jin-Tang [1 ,2 ]
机构
[1] Emory Univ, Dept Hematol & Med Oncol, Sch Med, Winship Canc Inst, Atlanta, GA 30322 USA
[2] Nankai Univ, Coll Life Sci, Dept Genet & Cell Biol, Tianjin 300071, Peoples R China
[3] Cent S Univ, Xiangya Hosp 2, Dept Pathol, Changsha, Hunan, Peoples R China
[4] Tianjin Med Univ, Canc Hosp, Dept Breast Canc Pathol, Key Lab Breast Canc Res, Tianjin, Peoples R China
[5] Tianjin Med Univ, Canc Hosp, Res Lab, Tianjin, Peoples R China
关键词
ESTROGEN-RECEPTOR-ALPHA; CLINICAL-IMPLICATIONS; MAMMARY-GLAND; SNORNA U50; EXPRESSION; TUMOR; GENE; SUBTYPES; CARCINOMAS; RESISTANCE;
D O I
10.1016/j.ajpath.2011.11.025
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Whereas estrogen-estrogen receptor alpha (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 T-47D and MDA-MB-361, suppressed cell growth in vitro and 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. (Am J Pathol 2012, 180: 1189-1201; DOI: 10.1016/j.ajpath.2011.11.025)
引用
收藏
页码:1189 / 1201
页数:13
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