Neuroglobin, a pro-survival player in estrogen receptor α-positive cancer cells

被引:47
作者
Fiocchetti, M. [1 ]
Nuzzo, M. T. [1 ]
Totta, P. [1 ]
Acconcia, F. [1 ]
Ascenzi, P. [2 ]
Marino, M. [1 ]
机构
[1] Univ Roma Tre, Dept Sci, I-00146 Rome, Italy
[2] Univ Roma Tre, Interdept Lab Elect Microscopy, I-00146 Rome, Italy
关键词
ER-BETA; SIGNAL-TRANSDUCTION; OXIDATIVE STRESS; 17-BETA-ESTRADIOL; EXPRESSION; CYTOGLOBIN; RESISTANCE; CARCINOMA; APOPTOSIS; PATHWAYS;
D O I
10.1038/cddis.2014.418
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Recently, we reported that human neuroglobin (NGB) is a new player in the signal transduction pathways that lead to 17 beta-estradiol (E2)-induced neuron survival. Indeed, E2 induces in neuron mitochondria the enhancement of NGB level, which in turn impairs the activation of a pro-apoptotic cascade. Nowadays, the existence of a similar pathway activated by E2 in non-neuronal cells is completely unknown. Here, the role of E2-induced NGB upregulation in tumor cells is reported. E2 induced the upregulation of NGB in a dose- and time-dependent manner in MCF-7, HepG2, SK-N-BE, and HeLa cells transfected with estrogen receptor alpha (ER alpha), whereas E2 was unable to modulate the NGB expression in the ER alpha-devoid HeLa cells. Both transcriptional and extranuclear ER alpha signals were required for the E2-dependent upregulation of NGB in MCF-7 and HepG2 cell lines. E2 stimulation modified NGB intracellular localization, inducing a significant reduction of NGB in the nucleus with a parallel increase of NGB in the mitochondria in both HepG2 and MCF-7 cells. Remarkably, E2 pretreatment did not counteract the H2O2-induced caspase-3 and poly (ADP-ribose) polymerase 1 (PARP-1) cleavage, as well as Bcl-2 overexpression in MCF-7 and HepG2 cells in which NGB was stably silenced by using shRNA lentiviral particles, highlighting the pivotal role of NGB in E2-induced antiapoptotic pathways in cancer cells. Present results indicate that the E2-induced NGB upregulation in cancer cells could represent a defense mechanism of E2-related cancers rendering them insensitive to oxidative stress. As a whole, these data open new avenues to develop therapeutic strategies against E2-related cancers.
引用
收藏
页码:e1449 / e1449
页数:10
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