Abstract
Ovarian cancer’s poor progression is closely associated with overexpression of matrix metalloproteinase 9 (MMP-9), which belongs to the class of enzymes believed to be involved in the degradation of extracellular matrix. However, the mechanisms underlying regulation of MMP-9 are not completely understood. STAT (signal transducer and activator of transcription) family of transcription factors is well known to be engaged in diverse cellular functions. Activation of STAT3 has been observed in a number of cancers, promoting tumorigenesis and metastasis via transcriptional activation of its target genes. In this study, we tested our hypothesis that STAT3 regulates MMP-9 gene expression in epithelial ovarian cancer. Using epithelial ovarian cancer cell lines as in vitro model, we show an abundance of phosphorylated STAT3 at Tyr705 (p-STAT3) in SKOV3 cell line. We further show that MMP-9 gene promoter was significantly enriched by p-STAT3, and IL-6 treatment led to a significant increase of MMP-9 at mRNA and protein levels, in addition to an association of p-STAT3 with MMP-9 gene. By using luciferase reporter assay, we determined that the STAT3 DNA responsive element of MMP-9 was sufficient to regulate transcriptional activity of a heterologous promoter. These results suggest that the phosphorylation of STAT3 regulates MMP-9 production in ovarian cancer, which might be responsible for its invasiveness and metastasis.
Highlights
Epithelial ovarian cancer (EOC) is one of the leading causes of cancer-related deaths in industrialized countries [1]
STAT3 regulates matrix metalloproteinase 9 (MMP-9) in epithelial ovarian cancer cell
We first determined the abundance of STAT3, phosphorylated STAT3 at Tyr705 (p-STAT3), and matrix metalloproteinase (MMP)-9 in ovarian cancer cells. 4 ovarian cancer cell lines were cultured for the analysis
Summary
Epithelial ovarian cancer (EOC) is one of the leading causes of cancer-related deaths in industrialized countries [1]. Despite advances in early diagnosis and treatment, the 5-year survival rate of ovarian cancer patients has not significantly improved. In the United States, a significantly high number of patients die of ovarian cancer each year [2]. This is due to lack of complete understanding of the etiological factors underlying ovarian carcinogenesis, local invasiveness and distant metastasis. The most commonly administered chemotherapy for the treatment of ovarian cancer is a combination of carboplatin and paclitaxel [3, 4]. Up to 80% of the patients initially respond well to this therapy [5, 6], a majority of patients suffer from recurrence and often die due to local and distant metastasis. Identification of novel drug targets and subsequent development of novel therapeutic approaches is needed
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
