PMID- 29959561
OWN - NLM
STAT- MEDLINE
DCOM- 20190917
LR  - 20200306
IS  - 1573-675X (Electronic)
IS  - 1360-8185 (Print)
IS  - 1360-8185 (Linking)
VI  - 23
IP  - 7-8
DP  - 2018 Aug
TI  - P53/PUMA are potential targets that mediate the protection of brain-derived 
      neurotrophic factor (BDNF)/TrkB from etoposide-induced cell death in 
      neuroblastoma (NB).
PG  - 408-419
LID - 10.1007/s10495-018-1467-6 [doi]
AB  - The over-expressions of brain-derived neurotrophic factor (BDNF) and its tyrosine 
      kinase receptor TrkB have been reported to induce chemo-resistance in 
      neuroblastoma (NB) cells. In this study, we investigated the roles of P53 and 
      BCL2 family members in the protection of BDNF/TrkB from etoposide-induced NB cell 
      death. TB3 and TB8, two tetracycline (TET)-regulated TrkB-expressing NB cell 
      lines, were utilized. The expressions of P53 and BCL2 family members were 
      detected by Western blot or RT-PCR. Transfection of siRNAs was used to knockdown 
      P53 or PUMA. Activated lentiviral was used to over-express PUMA. Cell survival 
      was performed by MTS assay, and the percentage of cell confluence was measured by 
      IncuCyte ZOOM. Our results showed that etoposide treatment induced significant 
      and time-dependent increase of P53, which could be blocked by pre-treatment with 
      BDNF, and knockdown P53 by transfecting siRNA attenuated etoposide-induced 
      TrkB-expressing NB cell death. PUMA was the most significantly changed BCL2 
      family member after treatment with etoposide, and pre-treatment with BDNF blocked 
      the increased expression of PUMA. Transfection with siRNA inhibited 
      etoposide-induced increased expression of PUMA, and attenuated etoposide-induced 
      NB cell death. We also found that over-expression of PUMA by infection of 
      activated lentiviral induced TrkB-expressing NB cell death in the absence of 
      etoposide, and treatment of BDNF protected NB cells from PUMA-induced cell death. 
      Our results suggested that P53 and PUMA may be potential targets that mediated 
      the protection of BDNF/TrkB from etoposide-induced NB cell death.
FAU - Hua, Zhongyan
AU  - Hua Z
AD  - Medical Research Center, Shengjing Hospital of China Medical University, #36 
      Sanhao Street, Heping District, Shenyang, 110004, China.
FAU - Zhan, Yue
AU  - Zhan Y
AD  - Medical Research Center, Shengjing Hospital of China Medical University, #36 
      Sanhao Street, Heping District, Shenyang, 110004, China.
FAU - Zhang, Simeng
AU  - Zhang S
AD  - Medical Research Center, Shengjing Hospital of China Medical University, #36 
      Sanhao Street, Heping District, Shenyang, 110004, China.
FAU - Dong, Yudi
AU  - Dong Y
AD  - Medical Research Center, Shengjing Hospital of China Medical University, #36 
      Sanhao Street, Heping District, Shenyang, 110004, China.
FAU - Jiang, Min
AU  - Jiang M
AD  - Medical Research Center, Shengjing Hospital of China Medical University, #36 
      Sanhao Street, Heping District, Shenyang, 110004, China.
FAU - Tan, Fei
AU  - Tan F
AD  - Department of Neurology, Shengjing Hospital of China Medical University, 
      Shenyang, China.
FAU - Liu, Zhihui
AU  - Liu Z
AD  - Cellular & Molecular Biology Section, Pediatric Oncology Branch, National Cancer 
      Institute, National Institutes of Health, Bethesda, MD, USA.
FAU - Thiele, Carol J
AU  - Thiele CJ
AD  - Cellular & Molecular Biology Section, Pediatric Oncology Branch, National Cancer 
      Institute, National Institutes of Health, Bethesda, MD, USA.
FAU - Li, Zhijie
AU  - Li Z
AD  - Medical Research Center, Shengjing Hospital of China Medical University, #36 
      Sanhao Street, Heping District, Shenyang, 110004, China. lizhijie68@hotmail.com.
LA  - eng
GR  - Z01 BC010789-01/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Apoptosis
JT  - Apoptosis : an international journal on programmed cell death
JID - 9712129
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 6PLQ3CP4P3 (Etoposide)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism/pharmacology
MH  - Cell Death/*drug effects
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Cisplatin/pharmacology
MH  - Drug Resistance, Neoplasm/genetics
MH  - Etoposide/*pharmacology
MH  - Humans
MH  - Neuroblastoma/genetics/*pathology
MH  - Tumor Suppressor Protein p53/drug effects/metabolism
PMC - PMC6294298
MID - NIHMS999488
OTO - NOTNLM
OT  - BDNF
OT  - Etoposide
OT  - Neuroblastoma
OT  - P53
OT  - PUMA
OT  - TrkB
COIS- Compliance with ethical standards Conflict of interest The authors declare no 
      conflict of interest.
EDAT- 2018/07/01 06:00
MHDA- 2019/09/19 06:00
PMCR- 2019/08/01
CRDT- 2018/07/01 06:00
PHST- 2018/07/01 06:00 [pubmed]
PHST- 2019/09/19 06:00 [medline]
PHST- 2018/07/01 06:00 [entrez]
PHST- 2019/08/01 00:00 [pmc-release]
AID - 10.1007/s10495-018-1467-6 [pii]
AID - 10.1007/s10495-018-1467-6 [doi]
PST - ppublish
SO  - Apoptosis. 2018 Aug;23(7-8):408-419. doi: 10.1007/s10495-018-1467-6.