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Article: p21-activated kinase-1 promotes aggressive phenotype, cell proliferation, and invasion in gestational trophoblastic disease

Titlep21-activated kinase-1 promotes aggressive phenotype, cell proliferation, and invasion in gestational trophoblastic disease
Authors
Issue Date2010
PublisherAmerican Society for Investigative Pathology. The Journal's web site is located at http://www.amjpathol.org
Citation
American Journal Of Pathology, 2010, v. 176 n. 6, p. 3015-3022 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/148622
ISSN
2014 Impact Factor: 4.591
2014 SCImago Journal Rankings: 2.259
PubMed Central ID
ISI Accession Number ID
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).

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorSiu, MKYen_HK
dc.contributor.authorYeung, MCWen_HK
dc.contributor.authorZhang, Hen_HK
dc.contributor.authorKong, DSHen_HK
dc.contributor.authorHo, JWKen_HK
dc.contributor.authorNgan, HYSen_HK
dc.contributor.authorChan, DCWen_HK
dc.contributor.authorCheung, ANYen_HK
dc.date.accessioned2012-05-29T06:14:10Z-
dc.date.available2012-05-29T06:14:10Z-
dc.date.issued2010en_HK
dc.identifier.citationAmerican Journal Of Pathology, 2010, v. 176 n. 6, p. 3015-3022en_HK
dc.identifier.issn0002-9440en_HK
dc.identifier.urihttp://hdl.handle.net/10722/148622-
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.en_HK
dc.languageengen_US
dc.publisherAmerican Society for Investigative Pathology. The Journal's web site is located at http://www.amjpathol.orgen_HK
dc.relation.ispartofAmerican Journal of Pathologyen_HK
dc.subject.meshAnimalsen_US
dc.subject.meshCell Lineen_US
dc.subject.meshCell Movement - Physiologyen_US
dc.subject.meshCell Proliferationen_US
dc.subject.meshFemaleen_US
dc.subject.meshGene Knockdown Techniquesen_US
dc.subject.meshGestational Ageen_US
dc.subject.meshGestational Trophoblastic Disease - Metabolism - Pathologyen_US
dc.subject.meshHumansen_US
dc.subject.meshIsoenzymes - Genetics - Metabolismen_US
dc.subject.meshPlacenta - Cytology - Metabolism - Pathologyen_US
dc.subject.meshPregnancyen_US
dc.subject.meshP21-Activated Kinases - Genetics - Metabolismen_US
dc.titlep21-activated kinase-1 promotes aggressive phenotype, cell proliferation, and invasion in gestational trophoblastic diseaseen_HK
dc.typeArticleen_HK
dc.identifier.emailSiu, MKY: mkysiu@hkucc.hku.hken_HK
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hken_HK
dc.identifier.emailCheung, ANY: anycheun@hkucc.hku.hken_HK
dc.identifier.authoritySiu, MKY=rp00275en_HK
dc.identifier.authorityNgan, HYS=rp00346en_HK
dc.identifier.authorityCheung, ANY=rp00542en_HK
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.2353/ajpath.2010.091263en_HK
dc.identifier.pmid20413688en_HK
dc.identifier.pmcidPMC2877861-
dc.identifier.scopuseid_2-s2.0-77953203982en_HK
dc.identifier.hkuros176674en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77953203982&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume176en_HK
dc.identifier.issue6en_HK
dc.identifier.spage3015en_HK
dc.identifier.epage3022en_HK
dc.identifier.isiWOS:000278689700042-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectAkt and p21-activated kinase signaling pathways in gestational trophoblastic disease-
dc.identifier.scopusauthoridSiu, MKY=24924018400en_HK
dc.identifier.scopusauthoridYeung, MCW=7101861644en_HK
dc.identifier.scopusauthoridZhang, H=8597830900en_HK
dc.identifier.scopusauthoridKong, DSH=36113859000en_HK
dc.identifier.scopusauthoridHo, JWK=36559246100en_HK
dc.identifier.scopusauthoridNgan, HYS=34571944100en_HK
dc.identifier.scopusauthoridChan, DCW=34767736800en_HK
dc.identifier.scopusauthoridCheung, ANY=54927484100en_HK

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