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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Qi, Mei Liu, Zhiyan Shen, Chengwu Wang, Lin Zeng, Jiping Wang, Chunni Li, Congcong Fu, Weiwei Sun, Yi Han, Bo |
| Description | Country affiliation: China Author Affiliation: Qi M ( Department of Pathology, Shandong University Medical School, Jinan, 250012, China.) |
| Abstract | ETS gene fusions involving ERG, ETV1, ETV4, ETV5, and FLI1 define a distinct class of prostate cancer (PCa), and this might have a bearing on diagnosis, prognosis, and rational therapeutic targeting. In the current study, we focused on the clinicopathological significance of ETV4 in Chinese PCa patients and the mechanisms whereby ETV4 overexpression mediates tumor invasion in the prostate. Overall, ETV4 overexpression was identified in 30.4 % (45/148) of PCa cases by immunohistochemistry. Accordingly, ETV4 was rearranged in only 1.6 % (2/128) of PCa patients. Clinically, ETV4 overexpression was significantly correlated with Gleason score (P = 0.045) and pathological tumor stage (P = 0.041). Multivariate Cox regression analysis indicated that ETV4 is an unfavorable independent prognostic factor (P = 0.040). Functional studies further showed that small interfering RNA (siRNA) knockdown of ETV4 significantly decreases proliferation and invasion of PC-3 cell and partially reverses epithelial-mesenchymal transition in vitro. Notably, ETV4 knockdown significantly downregulated expression of urokinase plasminogen activator (uPA) and its receptor (uPAR) at messenger RNA (mRNA) and protein levels. Chromatin immunoprecipitation assay demonstrated that ETV4 regulates uPA expression through direct binding to its promoter region. Additionally, ETV4 knockdown was also observed to significantly inhibit expression of matrix metalloproteinase (MMP)-2 and MMP-9. In conclusion, for the first time, our study suggested that ETV4 is an independent poor prognostic factor in Chinese PCa patients. Silencing of ETV4 suppresses invasion of PCa cells by inhibiting the expression of uPA/uPAR as well as MMPs. Further studies will be needed to determine whether ETV4 could be regarded as a potential target for the management and prevention of PCa. |
| File Format | HTM / HTML |
| ISSN | 10104283 |
| Issue Number | 5 |
| Volume Number | 36 |
| e-ISSN | 14230380 |
| Journal | Tumor Biology |
| Language | English |
| Publisher | Springer |
| Publisher Date | 2015-05-01 |
| Publisher Place | Netherlands |
| Access Restriction | Subscribed |
| Subject Keyword | Discipline Medicine__semicolon__oncology Adenovirus E1a Proteins Biosynthesis Matrix Metalloproteinase 2 Matrix Metalloproteinase 9 Prostatic Neoplasms Genetics Proto-oncogene Proteins Receptors, Urokinase Plasminogen Activator Urokinase-type Plasminogen Activator Aged Cell Line, Tumor Gene Expression Regulation, Neoplastic Drug Effects Gene Knockdown Techniques Humans Male Middle Aged Neoplasm Invasiveness Prognosis Pathology Rna, Small Interfering Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Cancer Research |
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