PMID- 25928539
OWN - NLM
STAT- MEDLINE
DCOM- 20160204
LR  - 20181202
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 4
DP  - 2015
TI  - Elevation of soluble guanylate cyclase suppresses proliferation and survival of 
      human breast cancer cells.
PG  - e0125518
LID - 10.1371/journal.pone.0125518 [doi]
LID - e0125518
AB  - Nitric oxide (NO) is an essential signaling molecule in biological systems. 
      Soluble guanylate cyclase (sGC), composing of alpha1 and beta1 subunit, is the receptor 
      for NO. Using radioimmunoassay, we discovered that activation of sGC by treatment 
      with bradykinin or sodium nitroprusside (SNP) is impaired in MCF-7 and MDA-MB-231 
      breast cancer cells as compared to normal breast epithelial 184A1 cells. The 
      184A1 cells expressed both sGC alpha1 and sGCbeta1 mRNAs. However, levels of sGCbeta1 mRNAs 
      were relatively lower in MCF-7 cells while both mRNA of sGC subunits were absent 
      in MDA-MB-231 cells. Treatment with DNA methyltransferase inhibitor 
      5-aza-2'-deoxycytidine (5-aza-dC) increased mRNA levels of both sGCalpha1 and sGCbeta1 
      in MDA-MB-231 cells but only sGCbeta1 mRNAs in MCF-7 cells. The 5-aza-dC treatment 
      increased the SNP-induced cGMP production in MCF-7 and MDA-MB-231, but not in 
      184A1 cells. Bisulfite sequencing revealed that the promoter of sGCalpha1 in 
      MDA-MB-231 cells and promoter of sGCbeta1 in MCF-7 cells were methylated. Promoter 
      hypermethylation of sGCalpha1 and sGCbeta1 was found in 1 out of 10 breast cancer 
      patients. Over-expression of both sGC subunits in MDA-MB-231 cells induced 
      apoptosis and growth inhibition in vitro as well as reduced tumor incidence and 
      tumor growth rate of MDA-MB-231 xenografts in nude mice. Elevation of sGC reduced 
      protein abundance of Bcl-2, Bcl-xL, Cdc2, Cdc25A, Cyclin B1, Cyclin D1, Cdk6, 
      c-Myc, and Skp2 while increased protein expression of p53. Our study demonstrated 
      that down-regulation of sGC, partially due to promoter methylation, provides 
      growth and survival advantage in human breast cancer cells.
FAU - Wen, Hui-Chin
AU  - Wen HC
AD  - Institute of Cellular and System Medicine, National Health Research Institutes, 
      Miaoli County, Taiwan.
FAU - Chuu, Chih-Pin
AU  - Chuu CP
AD  - Institute of Cellular and System Medicine, National Health Research Institutes, 
      Miaoli County, Taiwan.
FAU - Chen, Chen-Yu
AU  - Chen CY
AD  - Institute of Cellular and System Medicine, National Health Research Institutes, 
      Miaoli County, Taiwan.
FAU - Shiah, Shine-Gwo
AU  - Shiah SG
AD  - National Institute of Cancer Research, National Health Research Institutes, 
      Miaoli County, Taiwan.
FAU - Kung, Hsing-Jien
AU  - Kung HJ
AD  - Institute of Molecular and Genomic Medicine, National Health Research Institutes, 
      Miaoli County, Taiwan.
FAU - King, Kuang-Liang
AU  - King KL
AD  - Division of General Surgery, Department of Surgery, Taipei Veterans General 
      Hospital, Taipei City, Taiwan.
FAU - Su, Liang-Chen
AU  - Su LC
AD  - Institute of Cellular and System Medicine, National Health Research Institutes, 
      Miaoli County, Taiwan.
FAU - Chang, Shi-Chuan
AU  - Chang SC
AD  - Chest Department, Taipei Veterans General Hospital, Taipei City, Taiwan; 
      Institute of Emergency and Critical Care Medicine, National Yang-Ming University, 
      Taipei City, Taiwan.
FAU - Chang, Chung-Ho
AU  - Chang CH
AD  - Institute of Cellular and System Medicine, National Health Research Institutes, 
      Miaoli County, Taiwan; Graduate Institute of Basic Medical Science, Ph.D. Program 
      of Aging, China Medical University, Taichung City, Taiwan.
LA  - eng
GR  - P30 CA093373/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150430
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 169D1260KM (Nitroprusside)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 776B62CQ27 (Decitabine)
RN  - EC 4.6.1.2 (Guanylate Cyclase)
RN  - EC 4.6.1.2 (Soluble Guanylyl Cyclase)
RN  - H2D2X058MU (Cyclic GMP)
RN  - M801H13NRU (Azacitidine)
RN  - S8TIM42R2W (Bradykinin)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Azacitidine/analogs & derivatives/pharmacology
MH  - Bradykinin/pharmacology
MH  - Breast Neoplasms/genetics/*metabolism/therapy
MH  - Cell Cycle
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Cyclic GMP/*metabolism
MH  - DNA Methylation/genetics
MH  - Decitabine
MH  - Female
MH  - Guanylate Cyclase/genetics/*metabolism
MH  - Humans
MH  - MCF-7 Cells
MH  - Mice
MH  - Mice, Nude
MH  - Nitric Oxide/*metabolism
MH  - Nitroprusside/pharmacology
MH  - Promoter Regions, Genetic/genetics
MH  - Receptors, Cytoplasmic and Nuclear/genetics/*metabolism
MH  - Soluble Guanylyl Cyclase
PMC - PMC4416047
COIS- Competing Interests: Dr. Chih-Pin Chuu is a PLOS ONE Editorial Board member, 
      however, the authors' confirm that this does not alter their adherence to all the 
      PLOS ONE policies on sharing data and materials.
EDAT- 2015/05/01 06:00
MHDA- 2016/02/05 06:00
PMCR- 2015/04/30
CRDT- 2015/05/01 06:00
PHST- 2014/06/08 00:00 [received]
PHST- 2015/03/24 00:00 [accepted]
PHST- 2015/05/01 06:00 [entrez]
PHST- 2015/05/01 06:00 [pubmed]
PHST- 2016/02/05 06:00 [medline]
PHST- 2015/04/30 00:00 [pmc-release]
AID - PONE-D-14-25037 [pii]
AID - 10.1371/journal.pone.0125518 [doi]
PST - epublish
SO  - PLoS One. 2015 Apr 30;10(4):e0125518. doi: 10.1371/journal.pone.0125518. 
      eCollection 2015.