PMID- 29932870
OWN - NLM
STAT- Publisher
LR  - 20240227
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
DP  - 2018 Jun 22
TI  - ERalpha36 gene silencing promotes tau protein phosphorylation, inhibits cell 
      proliferation, and induces apoptosis in human neuroblastoma SH-SY5Y cells.
PG  - fj201701386
LID - 10.1096/fj.201701386 [doi]
AB  - Neuroblastoma is the most common cancer in infants and the third most common 
      cancer in children after leukemia and brain cancer. The purpose of our study was 
      to investigate the effects of estrogen receptor (ER)-alpha36 gene silencing on tau 
      protein phosphorylation, cell proliferation, and cell apoptosis in human 
      neuroblastoma SH-SY5Y cells. SH-SY5Y cells were treated with estrogen or left 
      untreated, to investigate the effects of estrogen stimulation on ERalpha36 and the 
      ERK/protein B kinase (AKT) signaling pathway. ERalpha36 mRNA expressions were 
      detected by quantitative RT-PCR. A phosphatase kit was used to test protein 
      phosphatase (PP)-2A activity before and after treatment. Western blot analysis 
      was conducted to detect protein expression of ERalpha36; tau protein; phosphorylated- 
      tau (p-tau) at site Thr231 [p-tau (Thr231)]; glycogen synthase kinase (GSK)3beta and 
      its specificity sites (Tyr216 and Ser9); Cyclin Dl; proliferating cell nuclear 
      antigen (PCNA); B-cell lymphoma (Bcl)-2; and Bcl-2-associated X protein (Bax). A 
      cell-counting kit (CCK)-8 assay was used to determine cell viability. Cell 
      apoptosis and rate of tumor growth and volume were determined by Annexin 
      V-FITC/PI staining and a xenotransplanted tumor model in nude mice. Results show 
      that without estrogen stimulation, ERalpha36 was inactivated. When stimulated by 
      estrogen, expression of ERalpha36, PP2A, p-GSK3beta (Ser9)/total protein ( t)-GSK3beta, 
      Cyclin Dl, PCNA, and Bcl-2 were up-regulated, and p-GSK3beta (Tyr216)/ t-GSK3beta 
      expression was down-regulated, as was p-tau (Thr231) and Bax expression. The 
      expression of p-ERK/ERK, p-AKT/AKT, p-methyl ethyl ketone (MEK)/MEK, and 
      p-mammalian target of rapamycin (mTOR)/mTOR expression was up-regulated, 
      suggesting that the ERK/AKT signaling pathway is activated. Cell proliferation 
      was also accelerated, whereas apoptosis was inhibited with stimulation by 
      estrogen. However, we found that the effects of silencing ERalpha36 on the expression 
      of related intracellular factors had no association with estrogen. Our study 
      demonstrates that ERalpha36 gene silencing can inhibit the activation of the ERK/AKT 
      signaling pathway, increase tau protein phosphorylation, decrease cell vitality 
      and tumorigenicity, and promote apoptosis of human neuroblastoma SH-SY5Y 
      cells.-Wang, H.-B., Li, T., Ma, D.-Z., Zhi, H. ERalpha36 gene silencing promotes tau 
      protein phosphorylation, inhibits cell proliferation, and induces apoptosis in 
      human neuroblastoma SH-SY5Y cells.
FAU - Wang, Hong-Bin
AU  - Wang HB
AD  - Department of Neurosurgery, Affiliated Hospital, Hebei University of Engineering, 
      Handan, China.
FAU - Li, Tao
AU  - Li T
AD  - Department of Neurosurgery, Affiliated Hospital, Hebei University of Engineering, 
      Handan, China.
FAU - Ma, Dong-Zhou
AU  - Ma DZ
AD  - Department of Neurosurgery, Affiliated Hospital, Hebei University of Engineering, 
      Handan, China.
FAU - Zhi, Hua
AU  - Zhi H
AD  - Department of Cardiology, Affiliated Hospital, Hebei University of Engineering, 
      Handan, China.
LA  - eng
PT  - Journal Article
DEP - 20180622
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
EDAT- 2018/06/23 06:00
MHDA- 2018/06/23 06:00
CRDT- 2018/06/23 06:00
PHST- 2018/06/23 06:00 [entrez]
PHST- 2018/06/23 06:00 [pubmed]
PHST- 2018/06/23 06:00 [medline]
AID - 10.1096/fj.201701386 [doi]
PST - aheadofprint
SO  - FASEB J. 2018 Jun 22:fj201701386. doi: 10.1096/fj.201701386.