Document Detail


Activation of mitogen-activated protein kinase is required for migration and invasion of placental site trophoblastic tumor.
MedLine Citation:
PMID:  16127165     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Martin Köbel; Gudrun Pohl; Wolfgang D Schmitt; Steffen Hauptmann; Tian-Li Wang; Ie-Ming Shih
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The American journal of pathology     Volume:  167     ISSN:  0002-9440     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-08-29     Completed Date:  2005-11-07     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  879-85     Citation Subset:  AIM; IM    
Affiliation:
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
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MeSH Terms
Descriptor/Qualifier:
Benzamides / 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:
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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