Global gene expression analysis reveals a link between NDRG1 and vesicle transport.
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.
Department of Medical Genetics, University of Oslo, Oslo, Norway ; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
Hanne A
HA
Askautrud
Department of Medical Genetics, University of Oslo, Oslo, Norway ; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
Elisabet
E
Gjernes
Department of Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science, Oslo, Norway.
Gjermund
G
Gunnes
Department of Medical Genetics, University of Oslo, Oslo, Norway ; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
Marit
M
Sletten
Clarient Diagnostic Services, Aliso Viejo, California, United States of America.
Douglas T
DT
Ross
Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
Anne Lise
AL
Børresen-Dale
Department of Medical Genetics, University of Oslo, Oslo, Norway ; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
Nina
N
Iversen
Department of Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science, Oslo, Norway.
Michael A
MA
Tranulis
Department of Medical Genetics, University of Oslo, Oslo, Norway ; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
Eirik
E
Frengen
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001692:Biological Transport / Q000235:genetics; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004317:Doxorubicin / Q000494:pharmacology; D020869:Gene Expression Profiling; D045325:HCT116 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D020411:Oligonucleotide Array Sequence Analysis; D015388:Organelles / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction / Q000235:genetics*; D000099259:N-myc Downstream-Regulated Gene 1 Protein
D018797:Cell Cycle Proteins; D004317:Doxorubicin; D047908:Intracellular Signaling Peptides and Proteins; D000099259:N-myc Downstream-Regulated Gene 1 Protein