論文 - 詳細
| RRC ID | 18641 |
|---|---|
| 著者 | Yeasmin S, Nakayama K, Rahman MT, Rahman M, Ishikawa M, Katagiri A, Iida K, Nakayama N, Miyazaki K. |
| タイトル | Loss of MKK4 expression in ovarian cancer: a potential role for the epithelial to mesenchymal transition. |
| ジャーナル | Int J Cancer |
| Abstract |
In the current study, we investigated the mechanism relating downregulation of mitogen-activated protein kinase kinase 4 (MKK4) expression to development of ovarian cancer. Over-expression of the MKK4 gene in TOV-21 G cells, a line with homozygous deletion of MKK4, resulted in morphologic changes in which cells growing in a scattered, fibroblast-like pattern formed tightly packed colonies. Based on a wound healing assay and a Matrigel invasion assay, we determined that both motility and invasiveness of MKK4-transfected TOV-21G cells were significantly reduced compared to control vector-transfected cells. To confirm that MKK4 expression related to tumor invasion resulted from an epithelial to mesenchymal transition (EMT)-like morphological change, we used 2 independent but complementary approaches. MKK4 gene knockdown in MDAH 2774 cells over-expressing MKK4 increased invasion activity. Additionally, engineered expression of MKK4 in SKOV3 cells, a line with low endogenous MKK4 expression, produced a phenotype similar to that of TOVG-21G. Interestingly, we found that MKK4 upregulation caused downregulation of phosphorylated NF-κB and Twist, as well as upregulation of E-cadherin, in TOVG-21G and SKOV3 cells. Reciprocal results were obtained in MDAH 2774 cells with MKK4 knockdown. Our results suggest that MKK4 downregulation causes increased phosphorylation NF-κB. This promotes Twist over-expression, resulting in E-cadherin downregulation that induces EMT in ovarian cancer. |
| 巻・号 | 128(1) |
| ページ | 94-104 |
| 公開日 | 2011-1-1 |
| DOI | 10.1002/ijc.25332 |
| PMID | 20309881 |
| MeSH | Animals Blotting, Western Cell Line, Tumor Cell Movement / genetics Disease Progression Epithelial-Mesenchymal Transition / genetics Female Gene Deletion Gene Expression Regulation, Enzymologic* Gene Expression Regulation, Neoplastic* Humans In Situ Hybridization, Fluorescence MAP Kinase Kinase 4 / genetics* MAP Kinase Kinase 4 / metabolism Mice Mice, Inbred BALB C Mice, Nude NF-kappa B / metabolism Neoplasms, Experimental / enzymology Neoplasms, Experimental / genetics Neoplasms, Experimental / pathology Ovarian Neoplasms / enzymology Ovarian Neoplasms / genetics* Ovarian Neoplasms / pathology Phosphorylation RNA Interference RNA, Small Interfering / genetics Reverse Transcriptase Polymerase Chain Reaction Transfection Transplantation, Heterologous |
| IF | 5.145 |
| 引用数 | 16 |
| WOS 分野 | ONCOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | JHOC-5(RCB1520) |