Askautrud Hanne A, Gjernes Elisabet, Gunnes Gjermund, Sletten Marit, Ross Douglas T, Børresen-Dale Anne Lise, Iversen Nina, Tranulis Michael A, Frengen Eirik
Department of Medical Genetics, University of Oslo, Oslo, Norway ; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
Department of Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science, Oslo, Norway.
PLoS One. 2014 Jan 31;9(1):e87268. doi: 10.1371/journal.pone.0087268. eCollection 2014.
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.
N-myc下游调控基因1（NDRG1）由缺氧和DNA损伤等细胞应激诱导，在人类中，种系突变会导致夏科-马里-图思病。然而，NDRG1的细胞作用尚未完全明确。此前研究表明，NDRG1在缺氧条件下介导阿霉素耐药，提示其在这些条件下对细胞存活起作用。我们发现，在常氧条件下，用阿霉素处理的表达NDRG1短发夹RNA（shRNA）的细胞凋亡减少，这表明在正常氧压下，乳腺上皮细胞凋亡需要NDRG1。此外，不同的细胞应激方案，如缺氧和阿霉素处理，通过不同的应激信号通路诱导NDRG1。为了确定NDRG1参与的生物学途径，我们进一步比较了异位过表达NDRG1的人乳腺上皮细胞与表达NDRG1 shRNA的细胞的表达谱。结果表明，NDRG1可能与囊泡运输有关。
