Linked Life Data

21325635

Source:http://linkedlifedata.com/resource/pubmed/id/21325635

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-5-4
pubmed:abstractText
Gestational trophoblastic disease (GTD) includes frankly malignant choriocarcinoma (CCA) and placental site trophoblastic tumor and potentially malignant hydatidiform mole. p21-Activated kinase (PAK) 4 promotes cell motility. This study investigated the role of PAK4 in the pathogenesis of GTD. PAK4 messenger RNA and protein expressions in clinical samples and cell lines of normal placentas and GTD were determined by quantitative real-time polymerase chain reaction and western blot, respectively. The effects of human chorionic gonadotropin (hCG) and phosphoinositide 3 kinase (PI3K) on the expression and activation of PAK4 were investigated by treating CCA JEG3 and JAR cells with anti-hCG antibody and PI3K inhibitor, respectively. The effects of PAK4 on CCA cell proliferation, migration and invasion were assessed by corresponding functional assays. We demonstrated overexpression of PAK4 in GTD and CCA cell lines at both RNA and protein level. hCG is one of the upstream regulators of PAK4 expression, whereas activation of PAK4 is PI3K/PKB dependent in JEG3 and JAR cells. Significant correlation was found between PAK4 expression and proliferation index minichromosome maintenance complex component 7 (P = 0.007). In JEG3 and JAR cells, stably transfected PAK4 increased proliferation, migration and invasion, whereas small interfering RNA knockdown of PAK4 decreased proliferation, migration and invasion along with downregulated CDK6 and membrane-type 1 matrix metalloproteinase (MT1-MMP) and upregulated p16. We further found PAK4-mediated transcription of MT1-MMP in CCA cells by luciferase reporter assay. Our results demonstrated for the first time that overexpressed PAK4 was involved in the pathogenesis of GTD, promoting proliferation and enhancing cell migration and invasion in CCA cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1460-2180
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
765-71
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:21325635-1-Phosphatidylinositol 4-Kinase, pubmed-meshheading:21325635-Apoptosis, pubmed-meshheading:21325635-Blotting, Western, pubmed-meshheading:21325635-Cell Adhesion, pubmed-meshheading:21325635-Cell Line, Tumor, pubmed-meshheading:21325635-Cell Movement, pubmed-meshheading:21325635-Cell Proliferation, pubmed-meshheading:21325635-Choriocarcinoma, pubmed-meshheading:21325635-Chorionic Gonadotropin, pubmed-meshheading:21325635-Female, pubmed-meshheading:21325635-Gestational Trophoblastic Disease, pubmed-meshheading:21325635-Humans, pubmed-meshheading:21325635-Immunoenzyme Techniques, pubmed-meshheading:21325635-Matrix Metalloproteinase 14, pubmed-meshheading:21325635-Pregnancy, pubmed-meshheading:21325635-RNA, Messenger, pubmed-meshheading:21325635-RNA, Small Interfering, pubmed-meshheading:21325635-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:21325635-Trophoblastic Neoplasms, pubmed-meshheading:21325635-Uterine Neoplasms, pubmed-meshheading:21325635-p21-Activated Kinases
pubmed:year
2011
pubmed:articleTitle
Overexpressed PAK4 promotes proliferation, migration and invasion of choriocarcinoma.
pubmed:affiliation
Departments of Pathology, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong, Special Administrative Region of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't