title: Role of ERRF, a novel ER-related nuclear factor, in the growth control of ER-positive human breast cancer cells.
abstract: 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 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.
authors.affiliation: Department of Genetics and Cell Biology, Nankai University College of Life Sciences, Tianjin, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Su
authors.affiliation: Department of Hematology and Medical Oncology, School of Medicine, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Pathology, Second Xiangya Hospital, Central South University, Hunan, China.
authors.forename: Songqing
authors.initials: S
authors.lastname: Fan
authors.affiliation: Department of Genetics and Cell Biology, Nankai University College of Life Sciences, Tianjin, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wu
authors.affiliation: Key Laboratory of Breast Cancer Research, Department of Breast Cancer Pathology and Research Laboratory, Cancer Hospital of Tianjin Medical University, Tianjin, China.
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Wang
authors.affiliation: Department of Genetics and Cell Biology, Nankai University College of Life Sciences, Tianjin, China.
authors.forename: Liya
authors.initials: L
authors.lastname: Fu
authors.affiliation: Department of Hematology and Medical Oncology, School of Medicine, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors.forename: Xue-Yuan
authors.initials: XY
authors.lastname: Dong
authors.affiliation: Department of Hematology and Medical Oncology, School of Medicine, Winship Cancer Institute, Emory University, Atlanta, Georgia.
authors.forename: Jianping Jenny
authors.initials: JJ
authors.lastname: Ni
authors.affiliation: Key Laboratory of Breast Cancer Research, Department of Breast Cancer Pathology and Research Laboratory, Cancer Hospital of Tianjin Medical University, Tianjin, China. Electronic address: fuli@tijmu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Fu
authors.affiliation: Department of Genetics and Cell Biology, Nankai University College of Life Sciences, Tianjin, China. Electronic address: zhuzhengmao@nankai.edu.cn.
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Genetics and Cell Biology, Nankai University College of Life Sciences, Tianjin, China; Department of Hematology and Medical Oncology, School of Medicine, Winship Cancer Institute, Emory University, Atlanta, Georgia. Electronic address: jtdong@nankai.edu.cn.
authors.forename: Jin-Tang
authors.initials: JT
authors.lastname: Dong
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D018734:Genes, erbB-2 / Q000235:genetics; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D034741:RNA, Small Interfering / Q000494:pharmacology; D014183:Transplantation, Heterologous; D015854:Up-Regulation
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C571667:SRARP protein, human