PMID- 27196739
OWN - NLM
STAT- MEDLINE
DCOM- 20170707
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 5
DP  - 2016
TI  - Inhibition of beta-Catenin to Overcome Endocrine Resistance in Tamoxifen-Resistant 
      Breast Cancer Cell Line.
PG  - e0155983
LID - 10.1371/journal.pone.0155983 [doi]
LID - e0155983
AB  - BACKGROUND: The beta-catenin signaling is important in cell growth and 
      differentiation and is frequently dysregulated in various cancers. The most 
      well-known mechanism of endocrine resistance is cross-talk between the estrogen 
      receptor (ER) and other growth factor signaling, such as 
      phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin 
      (mTOR) signaling pathway. In the present study, we investigated whether beta-catenin 
      could be a potential target to overcome endocrine resistance in breast cancer. 
      METHODS: We established tamoxifen-resistant (TamR) cell line via long-term 
      exposure of MCF-7 breast cancer cells to gradually increasing concentrations of 
      tamoxifen. The levels of protein expression and mRNA transcripts were determined 
      using western blot analysis and real-time quantitative PCR. The transcriptional 
      activity of beta-catenin was measured using luciferase activity assay. RESULTS: TamR 
      cells showed a mesenchymal phenotype, and exhibited a relatively decreased 
      expression of ER and increased expression of human epidermal growth factor 
      receptor 2 and the epidermal growth factor receptor. We confirmed that the 
      expression and transcriptional activity of beta-catenin were increased in TamR cells 
      compared with control cells. The expression and transcriptional activity of 
      beta-catenin were inhibited by beta-catenin small-molecule inhibitor, ICG-001 or 
      beta-catenin siRNA. The viability of TamR cells, which showed no change after 
      treatment with tamoxifen, was reduced by ICG-001 or beta-catenin siRNA. The 
      combination of ICG-001 and mTOR inhibitor, rapamycin, yielded an additive effect 
      on the inhibition of viability in TamR cells. CONCLUSION: These results suggest 
      that beta-catenin plays a role in tamoxifen-resistant breast cancer, and the 
      inhibition of beta-catenin may be a potential target in tamoxifen-resistant breast 
      cancer.
FAU - Won, Hye Sung
AU  - Won HS
AD  - Division of Medical Oncology, Department of Internal Medicine, College of 
      Medicine, The Catholic University of Korea, Seoul, Korea.
FAU - Lee, Kyung Mee
AU  - Lee KM
AD  - Division of Hematology-Oncology, Departments of Internal Medicine, Ewha Medical 
      Research Center, School of Medicine, Ewha Womans University, Seoul, Korea.
FAU - Oh, Ju Eon
AU  - Oh JE
AD  - Division of Hematology-Oncology, Departments of Internal Medicine, Ewha Medical 
      Research Center, School of Medicine, Ewha Womans University, Seoul, Korea.
FAU - Nam, Eun Mi
AU  - Nam EM
AD  - Division of Hematology-Oncology, Departments of Internal Medicine, Ewha Medical 
      Research Center, School of Medicine, Ewha Womans University, Seoul, Korea.
FAU - Lee, Kyoung Eun
AU  - Lee KE
AD  - Division of Hematology-Oncology, Departments of Internal Medicine, Ewha Medical 
      Research Center, School of Medicine, Ewha Womans University, Seoul, Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160519
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antineoplastic Agents, Hormonal)
RN  - 0 (Bridged Bicyclo Compounds, Heterocyclic)
RN  - 0 (Estrogen Antagonists)
RN  - 0 (ICG 001)
RN  - 0 (Pyrimidinones)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (beta Catenin)
RN  - 094ZI81Y45 (Tamoxifen)
SB  - IM
MH  - Antineoplastic Agents, Hormonal/*toxicity
MH  - Bridged Bicyclo Compounds, Heterocyclic/pharmacology
MH  - *Drug Resistance, Neoplasm
MH  - Estrogen Antagonists/*toxicity
MH  - Humans
MH  - MCF-7 Cells
MH  - Pyrimidinones/pharmacology
MH  - Receptors, Estrogen/genetics/metabolism
MH  - Tamoxifen/*toxicity
MH  - beta Catenin/antagonists & inhibitors/genetics/*metabolism
PMC - PMC4873201
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2016/05/20 06:00
MHDA- 2017/07/08 06:00
PMCR- 2016/05/19
CRDT- 2016/05/20 06:00
PHST- 2015/12/07 00:00 [received]
PHST- 2016/05/06 00:00 [accepted]
PHST- 2016/05/20 06:00 [entrez]
PHST- 2016/05/20 06:00 [pubmed]
PHST- 2017/07/08 06:00 [medline]
PHST- 2016/05/19 00:00 [pmc-release]
AID - PONE-D-15-53045 [pii]
AID - 10.1371/journal.pone.0155983 [doi]
PST - epublish
SO  - PLoS One. 2016 May 19;11(5):e0155983. doi: 10.1371/journal.pone.0155983. 
      eCollection 2016.