Cheng Jung-Chien, Chang Hsun-Ming, Leung Peter C K
Department of Obstetrics and Gynaecology, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, V5Z 4H4, Canada.
Oncotarget. 2017 Jul 27;8(49):85224-85233. doi: 10.18632/oncotarget.19626. eCollection 2017 Oct 17.
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.
卵巢低级别浆液性癌（LGSC）是一种罕见疾病，目前被认为是一种与高级别浆液性癌（HGSC）不同的实体，HGSC是上皮性卵巢癌最常见且恶性程度最高的形式。结缔组织生长因子（CTGF）是一种分泌型基质细胞蛋白，已证明它可通过与微环境中的多种分子相互作用来调节许多生物学功能。越来越多的证据表明，CTGF的异常表达与癌症的发生和发展有关。转化生长因子-β1（TGF-β1）是一种众所周知的分子，它能在不同类型的正常细胞和癌细胞中强烈上调CTGF的表达。我们之前的研究表明，TGF-β1可诱导LGSC细胞凋亡。然而，TGF-β1对LGSC中CTGF表达的影响尚待明确。此外，CTGF是否介导TGF-β1诱导的LGSC细胞凋亡仍不清楚。在本研究中，我们发现TGF-β1处理通过激活两种人LGSC细胞系中的SMAD3信号上调CTGF表达。此外，siRNA介导的CTGF敲低可减弱TGF-β1诱导的细胞凋亡。而且，我们的结果表明，CTGF敲低对TGF-β1诱导的细胞凋亡的抑制作用是通过下调SMAD3表达介导的。本研究证明了CTGF在介导TGF-β1对LGCS的促凋亡作用中起重要作用。
