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Connective tissue growth factor mediates TGF-β1-induced low-grade serous ovarian tumor cell apoptosis

Ovarian low-grade serous carcinoma (LGSC) is a rare disease and is now considered to be a distinct entity from high-grade serous carcinoma (HGSC), which is the most common and malignant form of epithelial ovarian cancer. Connective tissue growth factor (CTGF) is a secreted matricellular protein that...

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Autores principales: Cheng, Jung-Chien, Chang, Hsun-Ming, Leung, Peter C.K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689605/
https://www.ncbi.nlm.nih.gov/pubmed/29156715
http://dx.doi.org/10.18632/oncotarget.19626
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author Cheng, Jung-Chien
Chang, Hsun-Ming
Leung, Peter C.K.
author_facet Cheng, Jung-Chien
Chang, Hsun-Ming
Leung, Peter C.K.
author_sort Cheng, Jung-Chien
collection PubMed
description Ovarian low-grade serous carcinoma (LGSC) is a rare disease and is now considered to be a distinct entity from high-grade serous carcinoma (HGSC), which is the most common and malignant form of epithelial ovarian cancer. Connective tissue growth factor (CTGF) is a secreted matricellular protein that has been shown to modulate many biological functions by interacting with multiple molecules in the microenvironment. Increasing evidence indicates that aberrant expression of CTGF is associated with cancer development and progression. Transforming growth factor-β1 (TGF-β1) is a well-known molecule that can strongly up-regulate CTGF expression in different types of normal and cancer cells. Our previous study demonstrated that TGF-β1 induces apoptosis of LGSC cells. However, the effect of TGF-β1 on CTGF expression in LGSC needs to be defined. In addition, whether CTGF mediates TGF-β1-induced LGSC cell apoptosis remains unknown. In the present study, we show that TGF-β1 treatment up-regulates CTGF expression by activating SMAD3 signaling in two human LGSC cell lines. Additionally, siRNA-mediated CTGF knockdown attenuates TGF-β1-induced cell apoptosis. Moreover, our results show that the inhibitory effect of the CTGF knockdown on TGF-β1-induced cell apoptosis is mediated by down-regulating SMAD3 expression. This study demonstrates an important role for CTGF in mediating the pro-apoptotic effects of TGF-β1 on LGCS.
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spelling pubmed-56896052017-11-17 Connective tissue growth factor mediates TGF-β1-induced low-grade serous ovarian tumor cell apoptosis Cheng, Jung-Chien Chang, Hsun-Ming Leung, Peter C.K. Oncotarget Research Paper Ovarian low-grade serous carcinoma (LGSC) is a rare disease and is now considered to be a distinct entity from high-grade serous carcinoma (HGSC), which is the most common and malignant form of epithelial ovarian cancer. Connective tissue growth factor (CTGF) is a secreted matricellular protein that has been shown to modulate many biological functions by interacting with multiple molecules in the microenvironment. Increasing evidence indicates that aberrant expression of CTGF is associated with cancer development and progression. Transforming growth factor-β1 (TGF-β1) is a well-known molecule that can strongly up-regulate CTGF expression in different types of normal and cancer cells. Our previous study demonstrated that TGF-β1 induces apoptosis of LGSC cells. However, the effect of TGF-β1 on CTGF expression in LGSC needs to be defined. In addition, whether CTGF mediates TGF-β1-induced LGSC cell apoptosis remains unknown. In the present study, we show that TGF-β1 treatment up-regulates CTGF expression by activating SMAD3 signaling in two human LGSC cell lines. Additionally, siRNA-mediated CTGF knockdown attenuates TGF-β1-induced cell apoptosis. Moreover, our results show that the inhibitory effect of the CTGF knockdown on TGF-β1-induced cell apoptosis is mediated by down-regulating SMAD3 expression. This study demonstrates an important role for CTGF in mediating the pro-apoptotic effects of TGF-β1 on LGCS. Impact Journals LLC 2017-07-27 /pmc/articles/PMC5689605/ /pubmed/29156715 http://dx.doi.org/10.18632/oncotarget.19626 Text en Copyright: © 2017 Cheng et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Cheng, Jung-Chien
Chang, Hsun-Ming
Leung, Peter C.K.
Connective tissue growth factor mediates TGF-β1-induced low-grade serous ovarian tumor cell apoptosis
title Connective tissue growth factor mediates TGF-β1-induced low-grade serous ovarian tumor cell apoptosis
title_full Connective tissue growth factor mediates TGF-β1-induced low-grade serous ovarian tumor cell apoptosis
title_fullStr Connective tissue growth factor mediates TGF-β1-induced low-grade serous ovarian tumor cell apoptosis
title_full_unstemmed Connective tissue growth factor mediates TGF-β1-induced low-grade serous ovarian tumor cell apoptosis
title_short Connective tissue growth factor mediates TGF-β1-induced low-grade serous ovarian tumor cell apoptosis
title_sort connective tissue growth factor mediates tgf-β1-induced low-grade serous ovarian tumor cell apoptosis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689605/
https://www.ncbi.nlm.nih.gov/pubmed/29156715
http://dx.doi.org/10.18632/oncotarget.19626
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