title: N-myc downstream-regulated gene 2 expression is associated with glucose transport and correlated with prognosis in breast carcinoma.
abstract: BACKGROUND
  N-myc downstream-regulated gene 2 (NDRG2), a novel tumour suppressor and cell stress-related gene, is involved in many cell metabolic processes, such as hormone, ion and fluid metabolism. We investigated whether NDRG2 is involved in any glucose-dependent energy metabolism, as well as the nature of its correlation with breast carcinoma.
  
  
  METHODS
  The correlations between NDRG2 expression and glucose transporter 1 (GLUT1) expression in clinical breast carcinoma tissues were analysed. The effects of NDRG2 on glucose uptake were assessed in breast cancer cells and xenograft tumours. The consequences of NDRG2-induced regulation of GLUT1 at the transcription and translation levels and the interaction between NDRG2 and GLUT1 were examined.
  
  
  RESULTS
  Data derived from clinical breast carcinoma specimens revealed that (1) patients with high NDRG2 expression had better disease-free survival and overall survival than those with low NDRG2 expression and (2) NDRG2 expression was negatively correlated with GLUT1 expression in these breast carcinoma tissues. NDRG2 inhibited glucose uptake by promoting GLUT1 protein degradation without affecting GLUT1 transcription in both breast cancer cells and xenograft tumours. In addition, NDRG2 protein interacted and partly colocalised with GLUT1 protein in cell cytoplasm areas.
  
  
  CONCLUSIONS
  The results of our study support the notion that NDRG2 plays an important role in tumour glucose metabolism, in which GLUT1 is a likely candidate contributor to glucose uptake suppression and tumour growth. Targeting the actions of NDRG2 in cell glucose-dependent energy delivery may provide an attractive strategy for therapeutic intervention in human breast carcinoma.
authors.forename: Ji
authors.initials: J
authors.lastname: Ma
authors.forename: Wenchao
authors.initials: W
authors.lastname: Liu
authors.forename: Hang
authors.initials: H
authors.lastname: Guo
authors.forename: Shaoqing
authors.initials: S
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.forename: Xilin
authors.initials: X
authors.lastname: Du
authors.forename: Shixiong
authors.initials: S
authors.lastname: Lei
authors.forename: Wugang
authors.initials: W
authors.lastname: Hou
authors.forename: Lize
authors.initials: L
authors.lastname: Xiong
authors.forename: Libo
authors.initials: L
authors.lastname: Yao
authors.forename: Nanlin
authors.initials: N
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D051272:Glucose Transporter Type 1; C466228:NDRG2 protein, human; C495677:SLC2A1 protein, human; D025521:Tumor Suppressor Proteins; D005947:Glucose