PMID- 25036590
OWN - NLM
STAT- MEDLINE
DCOM- 20151130
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 7
DP  - 2014
TI  - BDNF is associated with SFRP1 expression in luminal and basal-like breast cancer 
      cell lines and primary breast cancer tissues: a novel role in tumor suppression?
PG  - e102558
LID - 10.1371/journal.pone.0102558 [doi]
LID - e102558
AB  - Secreted frizzled related protein 1 (SFRP1) functions as an important inhibitor 
      of the Wnt pathway and is a known tumor suppressor gene, which is epigenetically 
      silenced in a variety of tumors e.g. in breast cancer. However, it is still 
      unclear how SFRP1 exactly affects the Wnt pathway. Our aim was to decipher SFRP1 
      involvement in biochemical signaling in dependency of different breast cancer 
      subtypes and to identify novel SFRP1-regulated genes. We generated SFRP1 
      over-expressing in vitro breast cancer models, reflecting the two major subtypes 
      by using basal-like BT20 and luminal-like HER2-positive SKBR3 cells. DNA 
      microarray expression profiling of these models revealed that SFRP1 expression 
      potentially modulates Bone morphogenetic protein- and Smoothened signaling 
      (p<0.01), in addition to the known impact on Wnt signaling. Importantly, further 
      statistical analysis revealed that in dependency of the cancer subtype model 
      SFRP1 may affect the canonical and non-canonical Wnt pathway (p<0.01), 
      respectively. While SFRP1 re-expression generally mediated distinct patterns of 
      transcriptionally induced or repressed genes in BT20 and SKBR3 cells, brain 
      derived neurotrophic factor (BDNF) was identified as a SFRP1 induced gene in both 
      cell lines. Although BDNF has been postulated as a putative oncogene, the 
      co-regulation with SFRP1 indicates a potential suppressive function in breast 
      cancer. Indeed, a positive correlation between SFRP1 and BDNF protein expression 
      could be shown (p<0.001) in primary breast cancer samples. Moreover, TCGA dataset 
      based analysis clearly underscores that BDNF mRNA is down-regulated in primary 
      breast cancer samples predicting a poor prognosis of these patients. In line, we 
      functionally provide evidence that stable BDNF re-expression in basal-like BT20 
      breast cancer cells blocks tumor cell proliferation. Hence, our results suggest 
      that BDNF might rather mediate suppressive than promoting function in human 
      breast cancer whose mode of action should be addressed in future studies.
FAU - Huth, Laura
AU  - Huth L
AD  - Molecular Oncology Group, Institute of Pathology, Medical Faculty of the RWTH 
      Aachen University, Aachen, Germany.
FAU - Rose, Michael
AU  - Rose M
AD  - Molecular Oncology Group, Institute of Pathology, Medical Faculty of the RWTH 
      Aachen University, Aachen, Germany.
FAU - Kloubert, Veronika
AU  - Kloubert V
AD  - Molecular Oncology Group, Institute of Pathology, Medical Faculty of the RWTH 
      Aachen University, Aachen, Germany.
FAU - Winkens, Wiebke
AU  - Winkens W
AD  - Molecular Oncology Group, Institute of Pathology, Medical Faculty of the RWTH 
      Aachen University, Aachen, Germany.
FAU - Schlensog, Martin
AU  - Schlensog M
AD  - Molecular Oncology Group, Institute of Pathology, Medical Faculty of the RWTH 
      Aachen University, Aachen, Germany.
FAU - Hartmann, Arndt
AU  - Hartmann A
AD  - Institute of Pathology, University Hospital Erlangen, Erlangen, Germany.
FAU - Knuchel, Ruth
AU  - Knuchel R
AD  - Molecular Oncology Group, Institute of Pathology, Medical Faculty of the RWTH 
      Aachen University, Aachen, Germany.
FAU - Dahl, Edgar
AU  - Dahl E
AD  - Molecular Oncology Group, Institute of Pathology, Medical Faculty of the RWTH 
      Aachen University, Aachen, Germany.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140718
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (SFRP1 protein, human)
RN  - 7171WSG8A2 (BDNF protein, human)
SB  - IM
MH  - Brain-Derived Neurotrophic Factor/biosynthesis/genetics/*physiology
MH  - Breast Neoplasms/genetics/*metabolism/pathology
MH  - Cell Division
MH  - Cell Line, Tumor
MH  - Female
MH  - Gene Expression Profiling
MH  - *Genes, Tumor Suppressor
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/*physiology
MH  - Membrane Proteins/*physiology
MH  - Neoplasm Proteins/biosynthesis/genetics/*physiology
MH  - Oligonucleotide Array Sequence Analysis
MH  - Primary Cell Culture
MH  - Prognosis
MH  - Proportional Hazards Models
MH  - Recombinant Fusion Proteins/metabolism
MH  - Transfection
MH  - Wnt Signaling Pathway
PMC - PMC4103839
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/07/19 06:00
MHDA- 2015/12/15 06:00
PMCR- 2014/07/18
CRDT- 2014/07/19 06:00
PHST- 2014/02/18 00:00 [received]
PHST- 2014/06/19 00:00 [accepted]
PHST- 2014/07/19 06:00 [entrez]
PHST- 2014/07/19 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
PHST- 2014/07/18 00:00 [pmc-release]
AID - PONE-D-14-06293 [pii]
AID - 10.1371/journal.pone.0102558 [doi]
PST - epublish
SO  - PLoS One. 2014 Jul 18;9(7):e102558. doi: 10.1371/journal.pone.0102558. 
      eCollection 2014.