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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?

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...

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Detalles Bibliográficos
Autores principales: Huth, Laura, Rose, Michael, Kloubert, Veronika, Winkens, Wiebke, Schlensog, Martin, Hartmann, Arndt, Knüchel, Ruth, Dahl, Edgar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4103839/
https://www.ncbi.nlm.nih.gov/pubmed/25036590
http://dx.doi.org/10.1371/journal.pone.0102558
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author Huth, Laura
Rose, Michael
Kloubert, Veronika
Winkens, Wiebke
Schlensog, Martin
Hartmann, Arndt
Knüchel, Ruth
Dahl, Edgar
author_facet Huth, Laura
Rose, Michael
Kloubert, Veronika
Winkens, Wiebke
Schlensog, Martin
Hartmann, Arndt
Knüchel, Ruth
Dahl, Edgar
author_sort Huth, Laura
collection PubMed
description 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.
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spelling pubmed-41038392014-07-21 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? Huth, Laura Rose, Michael Kloubert, Veronika Winkens, Wiebke Schlensog, Martin Hartmann, Arndt Knüchel, Ruth Dahl, Edgar PLoS One Research Article 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. Public Library of Science 2014-07-18 /pmc/articles/PMC4103839/ /pubmed/25036590 http://dx.doi.org/10.1371/journal.pone.0102558 Text en © 2014 Huth et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Huth, Laura
Rose, Michael
Kloubert, Veronika
Winkens, Wiebke
Schlensog, Martin
Hartmann, Arndt
Knüchel, Ruth
Dahl, Edgar
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?
title 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?
title_full 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?
title_fullStr 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?
title_full_unstemmed 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?
title_short 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?
title_sort 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?
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4103839/
https://www.ncbi.nlm.nih.gov/pubmed/25036590
http://dx.doi.org/10.1371/journal.pone.0102558
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