scholarly journals Expression and Clinical Role of Protein of Regenerating Liver (PRL) Phosphatases in Ovarian Carcinoma

2011 ◽  
Vol 12 (2) ◽  
pp. 1133-1145 ◽  
Author(s):  
Reuven Reich ◽  
Shany Hadar ◽  
Ben Davidson
2018 ◽  
Vol 474 (2) ◽  
pp. 177-185 ◽  
Author(s):  
Marta Brunetti ◽  
Arild Holth ◽  
Ioannis Panagopoulos ◽  
Anne Cathrine Staff ◽  
Francesca Micci ◽  
...  

2020 ◽  
Vol 21 (15) ◽  
pp. 5237 ◽  
Author(s):  
Natalie Filippov-Levy ◽  
Reuven Reich ◽  
Ben Davidson

The objective of the present study was to analyze the biological and clinical role of the long non-coding RNA LOC642852 in ovarian carcinoma (OC). LOC642852 expression was analyzed in seven OC cell lines (OVCAR-3, OVCAR-8, OVCA 433, OVCA 429, OC 238, DOV13, ES-2) and 139 high-grade serous carcinoma (HGSC) specimens (85 effusions, 54 surgical specimens). Following LOC642852 knockout (KO) using the CRISPR/Cas9 system, OVCAR-8 HGSC cells were analyzed for spheroid formation, migration, invasion, proliferation, matrix metalloproteinase (MMP) activity, and expression of cell signaling proteins. OVCAR-8 cells with LOC642852 KO were significantly less motile and less invasive compared to controls, with no differences in spheroid formation, proliferation, or matrix metalloproteinase (MMP) activity. Total Akt and Erk levels were comparable in controls and KO cells, but their phosphorylation was significantly increased in the latter. In clinical specimens, LOC642852 was overexpressed in ovarian tumors and omental/peritoneal metastases compared to effusion specimens (p = 0.013). A non-significant trend for shorter overall (p = 0.109) and progression-free (p = 0.056) survival was observed in patients with HGSC effusions with high LOC642852 levels. Bioinformatics analysis showed potential roles for LOC642852 as part of the TLE3/miR-221-3p ceRNA network and in relation to the FGFR3 protein. In conclusion, LOC642852 inactivation via CRISPR/Cas9 affects cell signaling, motility, and invasion in HGSC cells. LOC642852 is differentially expressed in HGSC cells at different anatomical sites. Its potential role in regulating the TLE3/miR-221-3p ceRNA network and FGFR3 merits further research.


Tumor Biology ◽  
2009 ◽  
Vol 30 (1) ◽  
pp. 15-25 ◽  
Author(s):  
Gunhild M. Mælandsmo ◽  
Vivi Ann Flørenes ◽  
Mai T.P. Nguyen ◽  
Kjersti Flatmark ◽  
Ben Davidson

2007 ◽  
Vol 38 (7) ◽  
pp. 1030-1036 ◽  
Author(s):  
Ben Davidson ◽  
Aasmund Berner ◽  
Claes G. Trope' ◽  
Tian-Li Wang ◽  
Ie-Ming Shih

2008 ◽  
Vol 39 (1) ◽  
pp. 87-95 ◽  
Author(s):  
Ben Davidson ◽  
Rivka Hadar ◽  
Anat Schlossberg ◽  
Tamar Sternlicht ◽  
Ana Slipicevic ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Esther Channah Broner ◽  
Hadil Onallah ◽  
Tali Tavor Re’em ◽  
Ben Davidson ◽  
Reuven Reich

Objective. We recently reported on the expression and clinical role of molecules that mediate exosome secretion in high-grade serous carcinoma. In the present study, the biological role of these molecules was analyzed. Methods. OVCAR8 and ES-2 ovarian carcinoma cells were studied using a combination of CRISPR/Cas9 technology and two 3D in vitro models—spheroids emulating effusions and alginate scaffolds representing solid lesions. Isolation of exosomes was validated by electron microscopy. TSAP6, NSMASE2, RAB27A, and RAB27B mRNA and protein levels were analyzed using qRT-PCR and Western blotting, respectively. Tumor aggressiveness was studied in vitro using scratch assay, invasion assay, and matrix metalloproteinase (MMP) activity assay and in vivo using a mouse model. Results. In OVCAR8 cells, mRNA expression of TSAP6 and RAB27A was significantly higher in spheroids compared to scaffolds, whereas the opposite was true for NSMASE2 mRNA. In ES-2 cells, TSAP6 and RAB27B mRNA expression was significantly higher in spheroids versus scaffolds. In addition, nSMase2 and TSAP6 protein expression was significantly higher in scaffolds compared to spheroids. CRISPR-edited cells with silencing of NSMASE2, TSAP6, and RAB27A/B had reduced migration, invasion, and MMP activity. Additionally, knockout (KO) of these molecules resulted in significantly diminished exosome secretion. In vivo assay showed that when injected to mice, OVCAR8 RAB27A/B KO cells, as opposed to control OVCAR8 cells, did not form ascites or visible tumor lesions and had reduced MMP expression. Conclusion. The present study provides evidence that different models for culturing ovarian carcinoma cells affect the expression of molecules mediating exosome secretion and that these molecules have a tumor-promoting role. Silencing these molecules may consequently have therapeutic relevance in this cancer.


2006 ◽  
Vol 103 (3) ◽  
pp. 831-840 ◽  
Author(s):  
Michal Gorovetz ◽  
Mark Baekelandt ◽  
Aasmund Berner ◽  
Claes G. Trope' ◽  
Ben Davidson ◽  
...  

1996 ◽  
Vol 51 (3) ◽  
pp. 216-218 ◽  
Author(s):  
Rachel G. Klein
Keyword(s):  

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