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Article: p21-activated kinase-1 promotes aggressive phenotype, cell proliferation, and invasion in gestational trophoblastic disease
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Titlep21-activated kinase-1 promotes aggressive phenotype, cell proliferation, and invasion in gestational trophoblastic disease
 
AuthorsSiu, MKY1
Yeung, MCW1
Zhang, H1
Kong, DSH1
Ho, JWK1
Ngan, HYS1
Chan, DCW1
Cheung, ANY1
 
Issue Date2010
 
PublisherAmerican Society for Investigative Pathology. The Journal's web site is located at http://www.amjpathol.org
 
CitationAmerican Journal Of Pathology, 2010, v. 176 n. 6, p. 3015-3022 [How to Cite?]
DOI: http://dx.doi.org/10.2353/ajpath.2010.091263
 
AbstractGestational trophoblastic disease (GTD) includes hydatidiform mole (HM), which can develop persistent gestational trophoblastic neoplasia requiring chemotherapy; choriocarcinoma, which is a frankly malignant tumor; placental site trophoblastic tumor; and epithelioid trophoblastic tumor. p21-Activated kinases (PAKs) promote malignant tumor progression. Therefore, this study investigated PAK1, PAK2, and p-PAK2 Ser 20 in the pathogenesis of GTD. By real-time PCR, PAK1 mRNA was significantly higher in HMs, particularly metastatic HMs (P = 0.046) and HMs that developed persistent disease (P = 0.011), when compared with normal placentas. By immunohistochemistry, significantly increased cytoplasmic PAK1 immunoreactivity in cytotrophoblasts was also detected in HMs (P = 0.042) and choriocarcinomas (P = 0.003). In addition, HMs that developed persistent disease displayed higher PAK1 immunoreactivity than those that regressed (P = 0.016), and elevated PAK1 immunoreactivity was observed in placental site trophoblastic tumors. Indeed, there was significant positive correlation between PAK1 expression and the proliferative indices Ki-67 (P = 0.016) and MCM7 (P = 0.026). Moreover, higher PAK1 mRNA and protein expression was confirmed in the choriocarcinoma cell-lines JEG-3 and JAR; however, PAK2 mRNA and p-PAK2 immunoreactivity showed a similar expression pattern in normal first trimester placentas and GTD. Knockdown of PAK1 in JEG-3 and JAR reduced cell proliferation, migration, and invasion ability, up-regulated p16, and down-regulated vascular endothelial growth factor and MT1-MMP expression. This is the first report revealing the involvement of PAK1 in the pathogenesis and clinical progress of GTD. Copyright © American Society for Investigative Pathology.
 
ISSN0002-9440
2012 Impact Factor: 4.522
2012 SCImago Journal Rankings: 2.148
 
DOIhttp://dx.doi.org/10.2353/ajpath.2010.091263
 
ISI Accession Number IDWOS:000278689700042
Funding AgencyGrant Number
Research Grants Council of the Hong Kong Special Administrative RegionHKU 7503/06M
Funding Information:

Supported by funding from the Research Grants Council of the Hong Kong Special Administrative Region (HKU 7503/06M).

 
ReferencesReferences in Scopus
 
GrantsAkt and p21-activated kinase signaling pathways in gestational trophoblastic disease
 
DC FieldValue
dc.contributor.authorSiu, MKY
 
dc.contributor.authorYeung, MCW
 
dc.contributor.authorZhang, H
 
dc.contributor.authorKong, DSH
 
dc.contributor.authorHo, JWK
 
dc.contributor.authorNgan, HYS
 
dc.contributor.authorChan, DCW
 
dc.contributor.authorCheung, ANY
 
dc.date.accessioned2012-05-29T06:14:10Z
 
dc.date.available2012-05-29T06:14:10Z
 
dc.date.issued2010
 
dc.description.abstractGestational trophoblastic disease (GTD) includes hydatidiform mole (HM), which can develop persistent gestational trophoblastic neoplasia requiring chemotherapy; choriocarcinoma, which is a frankly malignant tumor; placental site trophoblastic tumor; and epithelioid trophoblastic tumor. p21-Activated kinases (PAKs) promote malignant tumor progression. Therefore, this study investigated PAK1, PAK2, and p-PAK2 Ser 20 in the pathogenesis of GTD. By real-time PCR, PAK1 mRNA was significantly higher in HMs, particularly metastatic HMs (P = 0.046) and HMs that developed persistent disease (P = 0.011), when compared with normal placentas. By immunohistochemistry, significantly increased cytoplasmic PAK1 immunoreactivity in cytotrophoblasts was also detected in HMs (P = 0.042) and choriocarcinomas (P = 0.003). In addition, HMs that developed persistent disease displayed higher PAK1 immunoreactivity than those that regressed (P = 0.016), and elevated PAK1 immunoreactivity was observed in placental site trophoblastic tumors. Indeed, there was significant positive correlation between PAK1 expression and the proliferative indices Ki-67 (P = 0.016) and MCM7 (P = 0.026). Moreover, higher PAK1 mRNA and protein expression was confirmed in the choriocarcinoma cell-lines JEG-3 and JAR; however, PAK2 mRNA and p-PAK2 immunoreactivity showed a similar expression pattern in normal first trimester placentas and GTD. Knockdown of PAK1 in JEG-3 and JAR reduced cell proliferation, migration, and invasion ability, up-regulated p16, and down-regulated vascular endothelial growth factor and MT1-MMP expression. This is the first report revealing the involvement of PAK1 in the pathogenesis and clinical progress of GTD. Copyright © American Society for Investigative Pathology.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationAmerican Journal Of Pathology, 2010, v. 176 n. 6, p. 3015-3022 [How to Cite?]
DOI: http://dx.doi.org/10.2353/ajpath.2010.091263
 
dc.identifier.doihttp://dx.doi.org/10.2353/ajpath.2010.091263
 
dc.identifier.epage3022
 
dc.identifier.hkuros176674
 
dc.identifier.isiWOS:000278689700042
Funding AgencyGrant Number
Research Grants Council of the Hong Kong Special Administrative RegionHKU 7503/06M
Funding Information:

Supported by funding from the Research Grants Council of the Hong Kong Special Administrative Region (HKU 7503/06M).

 
dc.identifier.issn0002-9440
2012 Impact Factor: 4.522
2012 SCImago Journal Rankings: 2.148
 
dc.identifier.issue6
 
dc.identifier.pmid20413688
 
dc.identifier.scopuseid_2-s2.0-77953203982
 
dc.identifier.spage3015
 
dc.identifier.urihttp://hdl.handle.net/10722/148622
 
dc.identifier.volume176
 
dc.languageeng
 
dc.publisherAmerican Society for Investigative Pathology. The Journal's web site is located at http://www.amjpathol.org
 
dc.publisher.placeUnited States
 
dc.relation.ispartofAmerican Journal of Pathology
 
dc.relation.projectAkt and p21-activated kinase signaling pathways in gestational trophoblastic disease
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAnimals
 
dc.subject.meshCell Line
 
dc.subject.meshCell Movement - Physiology
 
dc.subject.meshCell Proliferation
 
dc.subject.meshFemale
 
dc.subject.meshGene Knockdown Techniques
 
dc.subject.meshGestational Age
 
dc.subject.meshGestational Trophoblastic Disease - Metabolism - Pathology
 
dc.subject.meshHumans
 
dc.subject.meshIsoenzymes - Genetics - Metabolism
 
dc.subject.meshPlacenta - Cytology - Metabolism - Pathology
 
dc.subject.meshPregnancy
 
dc.subject.meshP21-Activated Kinases - Genetics - Metabolism
 
dc.titlep21-activated kinase-1 promotes aggressive phenotype, cell proliferation, and invasion in gestational trophoblastic disease
 
dc.typeArticle
 
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<contributor.author>Ngan, HYS</contributor.author>
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Author Affiliations
  1. The University of Hong Kong