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Conference Paper: Activation of PKB/AKT promotes cell survival and invasion in choriocarcinoma

TitleActivation of PKB/AKT promotes cell survival and invasion in choriocarcinoma
Authors
Issue Date2009
PublisherAmerican Association for Cancer Research.
Citation
The 100th Annual Meeting of the American Association for Cancer Research (AACR 2009), Denver, Colorado, USA, 18-22 April 2009, abstract no. 4106 How to Cite?
AbstractBackground: Activated phosphatidylinositol 3-kinase (PI3K) and its downstream serine/threonine protein kinase B (PKB)/AKT are important regulators of cell proliferation, apoptosis and invasion. The activation at Ser473 residue of PKB by phosphorylation (p-PKB Ser473) is required for its maximal activity. Dysregulation of PI3K/PKB signaling pathway has been found to be an important feature of many human malignancies. However, the role of activated PI3K/PKB in choriocarcinoma is not reported yet. In this study, we investigated the expression of p-PKB (Ser473) in gestational trophoblastic disease and the effects of inhibiting PI3K/PKB signaling pathway in choriocarcinoma. Methods: Choriocarcinoma cell lines JEG-3 and JAR were treated with PI3K inhibitor LY294002 and possible change in p-PKB (Ser473) expression was detected by Western Blot. The effects of activated PI3K/PKB on invasive activity, cell proliferation, apoptosis and cell cycle regulation in choriocarcinoma cells were determined by Matrigel invasion assay, MTT assay, TUNEL and flow cytometry, respectively. The expression of p-PKB (Ser473) in 96 clinical samples of normal placentas (n=30), hydatidiform moles (n=60) and choriocarcinomas (n=6) was also evaluated immunohistochemically. Results: After treating JEG-3 and JAR with PI3K inhibitor LY294002, significantly lower p-PKB (Ser473) but unchanged total PKB expressions was found compared with non-treated control. The invasive activity and viability of choriocarcinoma cells were significantly decreased. Cell cycle analysis by flow cytometry showed significant arrests in both G1/S and G2/M checkpoints with increased cell population in sub-G1 phase. The latter finding concurred with increased apoptosis in LY294002-treated cells by TUNEL assay. Immunohistochemical analysis in choriocarcinoma tissue samples confirmed significantly higher p-PKB (Ser473) expression comparing with that in placental and molar trophoblastic tissues (P<0.05). Furthermore, the immunohistochemical index of p-PKB (Ser473) inversely correlated with apoptotic index as assessed by TUNEL assay (P=0.001). Conclusion: We thus conclude that activation of PI3K/PKB signaling pathway is involved in the pathogenesis of choriocarcinoma. Activated PI3K/PKB signaling pathway promotes cell proliferation and invasion as well as reduces apoptosis by overcoming G1/S and G2/M checkpoints of the cell cycle. PI3K inhibitor may be a potential novel therapeutic target in choriocarcinomas resistant to conventional treatment.
DescriptionConference Theme: Science, Synergy and Success
Poster session: Carcinogenesis 6: Molecular Carcinogenesis and DNA Damage
Persistent Identifierhttp://hdl.handle.net/10722/63558

 

DC FieldValueLanguage
dc.contributor.authorZhang, Hen_HK
dc.contributor.authorSiu, MKYen_HK
dc.contributor.authorWong, ESYen_HK
dc.contributor.authorChan, HYen_HK
dc.contributor.authorNgan, HYSen_HK
dc.contributor.authorCheung, ANYen_HK
dc.date.accessioned2010-07-13T04:26:23Z-
dc.date.available2010-07-13T04:26:23Z-
dc.date.issued2009en_HK
dc.identifier.citationThe 100th Annual Meeting of the American Association for Cancer Research (AACR 2009), Denver, Colorado, USA, 18-22 April 2009, abstract no. 4106-
dc.identifier.urihttp://hdl.handle.net/10722/63558-
dc.descriptionConference Theme: Science, Synergy and Successen_HK
dc.descriptionPoster session: Carcinogenesis 6: Molecular Carcinogenesis and DNA Damage-
dc.description.abstractBackground: Activated phosphatidylinositol 3-kinase (PI3K) and its downstream serine/threonine protein kinase B (PKB)/AKT are important regulators of cell proliferation, apoptosis and invasion. The activation at Ser473 residue of PKB by phosphorylation (p-PKB Ser473) is required for its maximal activity. Dysregulation of PI3K/PKB signaling pathway has been found to be an important feature of many human malignancies. However, the role of activated PI3K/PKB in choriocarcinoma is not reported yet. In this study, we investigated the expression of p-PKB (Ser473) in gestational trophoblastic disease and the effects of inhibiting PI3K/PKB signaling pathway in choriocarcinoma. Methods: Choriocarcinoma cell lines JEG-3 and JAR were treated with PI3K inhibitor LY294002 and possible change in p-PKB (Ser473) expression was detected by Western Blot. The effects of activated PI3K/PKB on invasive activity, cell proliferation, apoptosis and cell cycle regulation in choriocarcinoma cells were determined by Matrigel invasion assay, MTT assay, TUNEL and flow cytometry, respectively. The expression of p-PKB (Ser473) in 96 clinical samples of normal placentas (n=30), hydatidiform moles (n=60) and choriocarcinomas (n=6) was also evaluated immunohistochemically. Results: After treating JEG-3 and JAR with PI3K inhibitor LY294002, significantly lower p-PKB (Ser473) but unchanged total PKB expressions was found compared with non-treated control. The invasive activity and viability of choriocarcinoma cells were significantly decreased. Cell cycle analysis by flow cytometry showed significant arrests in both G1/S and G2/M checkpoints with increased cell population in sub-G1 phase. The latter finding concurred with increased apoptosis in LY294002-treated cells by TUNEL assay. Immunohistochemical analysis in choriocarcinoma tissue samples confirmed significantly higher p-PKB (Ser473) expression comparing with that in placental and molar trophoblastic tissues (P<0.05). Furthermore, the immunohistochemical index of p-PKB (Ser473) inversely correlated with apoptotic index as assessed by TUNEL assay (P=0.001). Conclusion: We thus conclude that activation of PI3K/PKB signaling pathway is involved in the pathogenesis of choriocarcinoma. Activated PI3K/PKB signaling pathway promotes cell proliferation and invasion as well as reduces apoptosis by overcoming G1/S and G2/M checkpoints of the cell cycle. PI3K inhibitor may be a potential novel therapeutic target in choriocarcinomas resistant to conventional treatment.-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research.-
dc.relation.ispartofAnnual Meeting of the American Association for Cancer Research-
dc.titleActivation of PKB/AKT promotes cell survival and invasion in choriocarcinomaen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailSiu, MKY: mkysiu@hku.hken_HK
dc.identifier.emailWong, ESY: esywong@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_fulltext-
dc.identifier.hkuros166978en_HK
dc.identifier.spageabstract no. 4106-
dc.identifier.epageabstract no. 4106-
dc.publisher.placeUnited States-

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