title: Abundant NDRG2 Expression Is Associated with Aggressiveness and Unfavorable Patients' Outcome in Basal-Like Breast Cancer.
abstract: NDRG2, a member of the N-myc downstream-regulated gene family, is thought to be a putative tumor suppressor gene with promising clinical impact in breast cancer. Since breast cancer comprises heterogeneous intrinsic subtypes with distinct clinical outcomes we investigated the pivotal role of NDRG2 in basal-type breast cancers. Based on subtype classified tumor (n = 45) and adjacent normal tissues (n = 17) we examined NDRG2 mRNA expression and CpG-hypermethylation, whose significance was further validated by independent data sets from The Cancer Genome Atlas (TCGA). In addition, NDRG2 protein expression was evaluated immunohistochemically using a tissue micro array (TMA, n = 211). In vitro, we investigated phenotypic effects caused by NDRG2 silencing in the basal A-like HCC1806 as well as NDRG2 over-expression in basal A-like BT20 compared to luminal-type MCF7 breast cancer cells. Our tissue collections demonstrated an overall low NDRG2 mRNA expression in breast cancer subtypes compared to normal breast tissue in line with an increased CpG-hypermethylation in breast cancer tissue. Independent TCGA data sets verified a significant (P<0.001) expression loss of NDRG2 in breast tumors. Of interest, basal-like tumors more frequently retained abundant NDRG2 expression concordant with a lower CpG-hypermethylation. Unexpectedly, basal-like breast cancer revealed an association of NDRG2 expression with unfavorable patients' outcome. In line with this observation, in vitro experiments demonstrated reduced proliferation and migration rates (~20%) in HCC1806 cells following NDRG2 silencing. In contrast, NDRG2 over-expressing luminal-type MCF7 cells demonstrated a 26% decreased proliferation rate. Until now, this is the first study investigating the putative role of NDRG2 in depth in basal-type breast cancer. Our data indicate that the described putative tumor suppressive function of NDRG2 may be confined to luminal- and basal B-type breast cancers.
authors.affiliation: Molecular Oncology Group, Institute of Pathology, Medical Faculty of the RWTH Aachen University, Aachen, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Kloten
authors.affiliation: Molecular Oncology Group, Institute of Pathology, Medical Faculty of the RWTH Aachen University, Aachen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schlensog
authors.affiliation: Molecular Oncology Group, Institute of Pathology, Medical Faculty of the RWTH Aachen University, Aachen, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Eschenbruch
authors.affiliation: Molecular Oncology Group, Institute of Pathology, Medical Faculty of the RWTH Aachen University, Aachen, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: Gasthaus
authors.affiliation: Molecular Oncology Group, Institute of Pathology, Medical Faculty of the RWTH Aachen University, Aachen, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: Tiedemann
authors.affiliation: Molecular Oncology Group, Institute of Pathology, Medical Faculty of the RWTH Aachen University, Aachen, Germany.
authors.forename: Jolein
authors.initials: J
authors.lastname: Mijnes
authors.affiliation: Molecular Oncology Group, Institute of Pathology, Medical Faculty of the RWTH Aachen University, Aachen, Germany.
authors.forename: Timon
authors.initials: T
authors.lastname: Heide
authors.affiliation: Molecular Oncology Group, Institute of Pathology, Medical Faculty of the RWTH Aachen University, Aachen, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Braunschweig
authors.affiliation: Molecular Oncology Group, Institute of Pathology, Medical Faculty of the RWTH Aachen University, Aachen, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Knüchel
authors.affiliation: Molecular Oncology Group, Institute of Pathology, Medical Faculty of the RWTH Aachen University, Aachen, Germany.
authors.forename: Edgar
authors.initials: E
authors.lastname: Dahl
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C466228:NDRG2 protein, human; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins