PMID- 25069039
OWN - NLM
STAT- MEDLINE
DCOM- 20141111
LR  - 20211021
IS  - 1872-7980 (Electronic)
IS  - 0304-3835 (Print)
IS  - 0304-3835 (Linking)
VI  - 353
IP  - 2
DP  - 2014 Oct 28
TI  - Critical roles for nitric oxide and ERK in the completion of prosurvival 
      autophagy in 4OHTAM-treated estrogen receptor-positive breast cancer cells.
PG  - 290-300
LID - S0304-3835(14)00382-6 [pii]
LID - 10.1016/j.canlet.2014.07.031 [doi]
AB  - Autophagy is a mechanism of tamoxifen (TAM) resistance in ER-positive (ER+) 
      breast cancer cells. In this study, we showed in ER+ MCF7 cells that 
      4-hydroxytamoxifen (4OHTAM) induced cellular nitric oxide (NO) that negatively 
      regulates cellular superoxide (O2-) and cytotoxicity. 4OHTAM stimulated LC3 
      lipidation and formation of monodansylcadaverine (MDC)-labeled autophagic 
      vesicles dependent on O2-. Depletion of NO increased O2- and LC3 lipidation, yet 
      reduced formation of MDC-labeled autophagic vesicles. Instead, NO-depleted cells 
      formed remarkably large vacuoles with rims decorated by LC3. The vacuoles were 
      not labeled by MDC or the acidic lysosome-specific fluorescence dye acridine 
      orange (AO). The vacuoles were increased by the late stage autophagy inhibitor 
      chloroquine, which also increased LC3 lipidation. These results suggest NO is 
      required for proper autophagic vesicle formation or maturation at a step after 
      LC3 lipidation. In addition, 4OHTAM induced O2--dependent activation of ERK, 
      inhibition of which destabilized lysosomes/autolysosomes upon 4OHTAM treatment 
      and together with depletion of NO led to necrotic cell death. These results 
      suggest an essential role for endogenous NO and ERK activation in the completion 
      of pro-survival autophagy.
CI  - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved.
FAU - Duan, Lei
AU  - Duan L
AD  - Department of Anatomy and Cell Biology, Rush University Medical Center, 1750 W 
      Harrison Street, Chicago, IL 60612, USA. Electronic address: lei_duan@rush.edu.
FAU - Danzer, Brian
AU  - Danzer B
AD  - Department of Radiation Oncology, Rush University Medical Center, 1750 W Harrison 
      Street, Chicago, IL 60612, USA.
FAU - Levenson, Victor V
AU  - Levenson VV
AD  - Department of Radiation Oncology, Rush University Medical Center, 1750 W Harrison 
      Street, Chicago, IL 60612, USA.
FAU - Maki, Carl G
AU  - Maki CG
AD  - Department of Anatomy and Cell Biology, Rush University Medical Center, 1750 W 
      Harrison Street, Chicago, IL 60612, USA. Electronic address: carl_maki@rush.edu.
LA  - eng
GR  - R01 CA137598/CA/NCI NIH HHS/United States
GR  - 1R01CA137598-01A1/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140725
PL  - Ireland
TA  - Cancer Lett
JT  - Cancer letters
JID - 7600053
RN  - 0 (Antineoplastic Agents)
RN  - 0 (MAP1LC3A protein, human)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Receptors, Estrogen)
RN  - 094ZI81Y45 (Tamoxifen)
RN  - 17197F0KYM (afimoxifene)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (NOS2 protein, human)
RN  - EC 1.14.13.39 (NOS3 protein, human)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Autophagy
MH  - Breast Neoplasms
MH  - Extracellular Signal-Regulated MAP Kinases/*physiology
MH  - Female
MH  - Humans
MH  - MAP Kinase Signaling System
MH  - MCF-7 Cells
MH  - Microtubule-Associated Proteins/metabolism
MH  - Nitric Oxide/*physiology
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Nitric Oxide Synthase Type III/metabolism
MH  - Oxygen/metabolism
MH  - Phagosomes/metabolism
MH  - Protein Processing, Post-Translational
MH  - Receptors, Estrogen/*metabolism
MH  - Tamoxifen/*analogs & derivatives/pharmacology
PMC - PMC4827626
MID - NIHMS616788
OTO - NOTNLM
OT  - Autophagy
OT  - Breast cancer
OT  - Estrogen receptor
OT  - Nitric oxide
OT  - Reactive oxygen species
OT  - Tamoxifen
COIS- Conflict of interest statement: The authors have no conflicts of interest to 
      state, personal, financial, or otherwise.
EDAT- 2014/07/30 06:00
MHDA- 2014/11/12 06:00
PMCR- 2016/04/11
CRDT- 2014/07/29 06:00
PHST- 2014/05/01 00:00 [received]
PHST- 2014/07/16 00:00 [revised]
PHST- 2014/07/19 00:00 [accepted]
PHST- 2014/07/29 06:00 [entrez]
PHST- 2014/07/30 06:00 [pubmed]
PHST- 2014/11/12 06:00 [medline]
PHST- 2016/04/11 00:00 [pmc-release]
AID - S0304-3835(14)00382-6 [pii]
AID - 10.1016/j.canlet.2014.07.031 [doi]
PST - ppublish
SO  - Cancer Lett. 2014 Oct 28;353(2):290-300. doi: 10.1016/j.canlet.2014.07.031. Epub 
      2014 Jul 25.