title: GGNBP2 acts as a tumor suppressor by inhibiting estrogen receptor α activity in breast cancer cells.
abstract: Gametogenetin-binding protein 2 (GGNBP2) is encoded in human chromosome 17q12-q23, a region known as a breast and ovarian cancer susceptibility locus. GGNBP2, also referred to ZFP403, has a single C2H2 zinc finger and a consensus LxxLL nuclear receptor-binding motif. Here, we demonstrate that GGNBP2 expression is reduced in primary human breast tumors and in breast cancer cell lines, including T47D, MCF-7, LCC9, LY2, and MDA-MB-231 compared with normal, immortalized estrogen receptor α (ERα) negative MCF-10A and MCF10F breast epithelial cells. Overexpression of GGNBP2 inhibits the proliferation of T47D and MCF-7 ERα positive breast cancer cells without affecting MCF-10A and MCF10F. Stable GGNBP2 overexpression in T47D cells inhibits 17β-estradiol (E2)-stimulated proliferation as well as migration, invasion, anchorage-independent growth in vitro, and xenograft tumor growth in mice. We further demonstrate that GGNBP2 protein physically interacts with ERα, inhibits E2-induced activation of estrogen response element-driven reporter activity, and attenuates ER target gene expression in T47D cells. In summary, our in vitro and in vivo findings suggest that GGNBP2 is a novel breast cancer tumor suppressor functioning as a nuclear receptor corepressor to inhibit ERα activity and tumorigenesis.
authors.affiliation: Division of Life Sciences, Center for Nutrigenomics & Applied Animal Nutrition, Alltech Inc., Nicholasville, KY, 40356, USA.
authors.forename: Zi-Jian
authors.initials: ZJ
authors.lastname: Lan
authors.affiliation: The 3rd Department of Breast Cancer, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute & Hospital, 500 South Preston Street, Hu-Xi District, 300060, Tianjin, People's Republic of China.
authors.forename: YunHui
authors.initials: Y
authors.lastname: Hu
authors.affiliation: The 3rd Department of Breast Cancer, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute & Hospital, 500 South Preston Street, Hu-Xi District, 300060, Tianjin, People's Republic of China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of OB/GYN & Women's Health, University of Louisville Health Sciences Center, 500 South Preston Street, Louisville, KY, 40292, USA.
authors.forename: Xian
authors.initials: X
authors.lastname: Li
authors.affiliation: Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, University of Louisville Health Sciences Center, Louisville, KY, 40292, USA.
authors.forename: Huaxin
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, University of Louisville Health Sciences Center, Louisville, KY, 40292, USA.
authors.forename: Jixiang
authors.initials: J
authors.lastname: Ding
authors.affiliation: Department of Biochemistry & Molecular Genetics, University of Louisville Health Sciences Center, Louisville, KY, 40292, USA.
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Klinge
authors.affiliation: Department of Biochemistry & Molecular Genetics, University of Louisville Health Sciences Center, Louisville, KY, 40292, USA.
authors.forename: Brandie N
authors.initials: BN
authors.lastname: Radde
authors.affiliation: Department of Pediatrics, The University of Texas at Austin Dell Medical School, Austin, TX, 78712, USA.
authors.forename: Austin J
authors.initials: AJ
authors.lastname: Cooney
authors.affiliation: The 3rd Department of Breast Cancer, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute & Hospital, 500 South Preston Street, Hu-Xi District, 300060, Tianjin, People's Republic of China. zhangjin@tjmuch.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of OB/GYN & Women's Health, University of Louisville Health Sciences Center, 500 South Preston Street, Louisville, KY, 40292, USA. zhenmin.lei@louisville.edu.
authors.forename: Zhenmin
authors.initials: Z
authors.lastname: Lei
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D009368:Neoplasm Transplantation; D020218:Response Elements / Q000187:drug effects; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C487856:GGNBP2 protein, human; D025521:Tumor Suppressor Proteins; D004958:Estradiol
keywords: Breast cancer; ERα; GGNBP2; Tumor suppressor; Tumorigenesis