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
2011 Impact Factor: 4.89
2011 SCImago Journal Rankings: 0.697
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 Field
Value
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.grantAkt and p21-activated kinase signaling pathways in gestational trophoblastic disease
dc.description.grantcode82405
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
2011 Impact Factor: 4.89
2011 SCImago Journal Rankings: 0.697
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.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
Author Affiliations
  1. The University of Hong Kong