Global gene expression analysis reveals a link between NDRG1 and vesicle transport

PLoS One. 2014 Jan 31;9(1):e87268. doi: 10.1371/journal.pone.0087268. eCollection 2014.

Abstract

N-myc downstream-regulated gene 1 (NDRG1) is induced by cellular stress such as hypoxia and DNA damage, and in humans, germ line mutations cause Charcot-Marie-Tooth disease. However, the cellular roles of NDRG1 are not fully understood. Previously, NDRG1 was shown to mediate doxorubicin resistance under hypoxia, suggesting a role for NDRG1 in cell survival under these conditions. We found decreased apoptosis in doxorubicin-treated cells expressing NDRG1 shRNAs under normoxia, demonstrating a requirement for NDRG1 in apoptosis in breast epithelial cells under normal oxygen pressure. Also, different cellular stress regimens, such as hypoxia and doxorubicin treatment, induced NDRG1 through different stress signalling pathways. We further compared expression profiles in human breast epithelial cells ectopically over-expressing NDRG1 with cells expressing NDRG1 shRNAs in order to identify biological pathways where NDRG1 is involved. The results suggest that NDRG1 may have roles connected to vesicle transport.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Biological Transport / genetics
  • Blotting, Western
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Doxorubicin / pharmacology
  • Gene Expression Profiling*
  • HCT116 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • MCF-7 Cells
  • Microscopy, Confocal
  • Oligonucleotide Array Sequence Analysis
  • Organelles / genetics*
  • Organelles / metabolism
  • RNA Interference
  • Signal Transduction / genetics*

Substances

  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • N-myc downstream-regulated gene 1 protein
  • Doxorubicin

Associated data

  • GEO/GSE33439

Grants and funding

This work was supported by The Research Council of Norway through grants from the Functional Genomics Program (FUGE, grant number 151882) and project support (grant number 160698/V40), and from Southeastern Regional Health Authorities (grant number 2007060). EF and HAA were supported by “University of Oslo Research Fund (UNIFOR)” and Ullevål University Hospital Research Fund (VIRUUS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.