| Activation of mitogen-activated protein kinase is required for migration and invasion of placental site trophoblastic tumor. | |
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MedLine Citation:
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PMID: 16127165 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Placental site trophoblastic tumor (PSTT) is a gestational neoplasm derived from the extravillous (intermediate) trophoblast of the implantation site. PSTT is characterized by a highly invasive phenotype, but the molecular mechanisms are poorly understood. In this report, we demonstrate that PSTTs expressed the activated (phosphorylated) form of mitogen-activated protein kinase (MAPK) in 84% of cases, whereas the normal extravillous trophoblastic cells did not. To characterize the role of MAPK activation in PSTT, we established the first PSTT cell culture, IST-2, from a surgically resected PSTT. IST-2 cells expressed HLA-G and Mel-CAM but not E-cadherin, an immunophenotype characteristic of PSTT. IST-2 cells were highly motile and invasive in culture as compared to choriocarcinoma JEG-3 cells and normal extravillous trophoblastic cells. Based on wound assay, time-lapse videomicroscopy for cell tracking, and invasion chamber assays, we found that the motility and invasion of IST-2 cells were significantly reduced (P<0.01) after treatment with the MEK inhibitors CI-1040 and PD 59089, which prevent activation of MAPK. In contrast, neither compound had any effect on normal extravillous trophoblastic cells or JEG-3 cells. In conclusion, our findings demonstrate a functional role of MAPK activation in the motility and invasion of PSTT. |
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Authors:
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Martin Köbel; Gudrun Pohl; Wolfgang D Schmitt; Steffen Hauptmann; Tian-Li Wang; Ie-Ming Shih |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: The American journal of pathology Volume: 167 ISSN: 0002-9440 ISO Abbreviation: Am. J. Pathol. Publication Date: 2005 Sep |
Date Detail:
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Created Date: 2005-08-29 Completed Date: 2005-11-07 Revised Date: 2013-06-03 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 879-85 Citation Subset: AIM; IM |
Affiliation:
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Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Benzamides
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pharmacology Case-Control Studies Cell Movement* Cells, Cultured Enzyme Activation Female Flavonoids / pharmacology Humans Mitogen-Activated Protein Kinases / antagonists & inhibitors, metabolism* Neoplasm Invasiveness Pregnancy Protein Kinase Inhibitors / pharmacology Trophoblastic Tumor, Placental Site / enzymology, pathology*, physiopathology* Trophoblasts / enzymology Uterine Neoplasms / enzymology, pathology*, physiopathology* |
| Chemical | |
Reg. No./Substance:
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0/2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; 0/2-(2-chloro-4-iodophenylamino)-N-cyclopropylmethoxy-3,4-difluorobenzamide; 0/Benzamides; 0/Flavonoids; 0/Protein Kinase Inhibitors; EC 2.7.11.24/Mitogen-Activated Protein Kinases |
| Comments/Corrections | |
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