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Conference Paper: Dysregulated expression of stem cell transcription factor Nanog in development and progress of ovarian cancers

TitleDysregulated expression of stem cell transcription factor Nanog in development and progress of ovarian cancers
Authors
Issue Date2010
PublisherAmerican Association for Cancer Research.
Citation
The 101st Annual Meeting of the American Association for Cancer Research (AACR 2010), Washington D.C., 17-21 April 2010. How to Cite?
AbstractIntroduction: Ovarian cancer is the most lethal of all gynecological malignacies due to its lack of symptoms at early stages. In addition, widespread intraperitoneal metastases and malignant ascites frequently develop. Therefore, it is very important to identify novel prognostic and therapeutic targets for this cancer. Many researchers believe that only a small subset of cancer cells are endowed with stem cell properties, which are responsible for tumor growth, metastatic progression and recurrence. Nanog is one of core transcription factors essential for the maintaining self-renewal and pluripotency in stem cells. This study investigated the clinical significance, functional roles and putative downstream targets of Nanog in ovarian cancer. Methods and Results: Differential protein expression profile of Nanog in clinical samples, including benign (n=6), borderline (n=7), carcinomas (n=97) and metastatic foci (n=24) were determined by immunohistochemistry. Differential mRNA expression pattern of Nanog in 3 normal ovarian epithelial cell lines, 16 ovarian cancer cell lines was assessed by quantitative real-time polymerase chain reaction. Subcellular localization of Nanog was performed by Western blotting. Nanog was found to be localized in the nucleus of ovarian cancers. High Nanog expression in ovarian cancers was significantly associated with high grade tumors, serous histological type and chemoresistance (p<0.05). Importantly, Nanog was found to be highly expressed in ovarian cancer cell lines with metastasis-associated property and in clinical samples of metastatic foci. Elevated Nanog expression was associated with poor overall and disease-free survival in the univariate analysis. Nanog expression became one of the independent prognostic factors in the multivariate analysis for overall but not disease-free survival. By Transwell migration and invasion assays, stable knockdown of Nanog in ovarian cancer cell line, OVCAR-3, impeded cell migration and invasion. Stable knockdown of Nanog also increased mRNA expression of E-cadherin (an essential epithelial mesenchymal transition marker, thus related to metastasis) and FOXO1A (an important gene related to chemoresistance). Conclusion: Nanog was associated with progression of ovarian tumors, patients’ overall survival and chemoresistance, suggesting that Nanog can be one of the potential prognostic markers and therapeutic molecular targets in ovarian cancer.
DescriptionPoster Session 14 - PO.TB02.05: Cancer Stem Cell Biology 1: abstract no. 4233
Persistent Identifierhttp://hdl.handle.net/10722/129868

 

DC FieldValueLanguage
dc.contributor.authorSiu, MKYen_US
dc.contributor.authorWong, ESYen_US
dc.contributor.authorKong, DSHen_US
dc.contributor.authorWong, OGWen_US
dc.contributor.authorTam, KFen_US
dc.contributor.authorNgan, HYSen_US
dc.contributor.authorLe, XFen_US
dc.contributor.authorCheung, ANYen_US
dc.date.accessioned2010-12-23T08:43:24Z-
dc.date.available2010-12-23T08:43:24Z-
dc.date.issued2010en_US
dc.identifier.citationThe 101st Annual Meeting of the American Association for Cancer Research (AACR 2010), Washington D.C., 17-21 April 2010.en_US
dc.identifier.urihttp://hdl.handle.net/10722/129868-
dc.descriptionPoster Session 14 - PO.TB02.05: Cancer Stem Cell Biology 1: abstract no. 4233-
dc.description.abstractIntroduction: Ovarian cancer is the most lethal of all gynecological malignacies due to its lack of symptoms at early stages. In addition, widespread intraperitoneal metastases and malignant ascites frequently develop. Therefore, it is very important to identify novel prognostic and therapeutic targets for this cancer. Many researchers believe that only a small subset of cancer cells are endowed with stem cell properties, which are responsible for tumor growth, metastatic progression and recurrence. Nanog is one of core transcription factors essential for the maintaining self-renewal and pluripotency in stem cells. This study investigated the clinical significance, functional roles and putative downstream targets of Nanog in ovarian cancer. Methods and Results: Differential protein expression profile of Nanog in clinical samples, including benign (n=6), borderline (n=7), carcinomas (n=97) and metastatic foci (n=24) were determined by immunohistochemistry. Differential mRNA expression pattern of Nanog in 3 normal ovarian epithelial cell lines, 16 ovarian cancer cell lines was assessed by quantitative real-time polymerase chain reaction. Subcellular localization of Nanog was performed by Western blotting. Nanog was found to be localized in the nucleus of ovarian cancers. High Nanog expression in ovarian cancers was significantly associated with high grade tumors, serous histological type and chemoresistance (p<0.05). Importantly, Nanog was found to be highly expressed in ovarian cancer cell lines with metastasis-associated property and in clinical samples of metastatic foci. Elevated Nanog expression was associated with poor overall and disease-free survival in the univariate analysis. Nanog expression became one of the independent prognostic factors in the multivariate analysis for overall but not disease-free survival. By Transwell migration and invasion assays, stable knockdown of Nanog in ovarian cancer cell line, OVCAR-3, impeded cell migration and invasion. Stable knockdown of Nanog also increased mRNA expression of E-cadherin (an essential epithelial mesenchymal transition marker, thus related to metastasis) and FOXO1A (an important gene related to chemoresistance). Conclusion: Nanog was associated with progression of ovarian tumors, patients’ overall survival and chemoresistance, suggesting that Nanog can be one of the potential prognostic markers and therapeutic molecular targets in ovarian cancer.-
dc.languageengen_US
dc.publisherAmerican Association for Cancer Research.-
dc.relation.ispartofAnnual Meeting of the American Association for Cancer Research-
dc.titleDysregulated expression of stem cell transcription factor Nanog in development and progress of ovarian cancersen_US
dc.typeConference_Paperen_US
dc.identifier.emailSiu, MKY: mkysiu@hku.hken_US
dc.identifier.emailWong, ESY: esywong@hkucc.hku.hken_US
dc.identifier.emailKong, DSH: dankong@hkusua.hku.hken_US
dc.identifier.emailWong, OGW: wonggw@hkucc.hku.hken_US
dc.identifier.emailTam, KF: tamkf@hkucc.hku.hken_US
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hken_US
dc.identifier.emailCheung, ANY: anycheun@hkucc.hku.hk-
dc.identifier.authoritySiu, MKY=rp00275en_US
dc.identifier.authorityNgan, HYS=rp00346en_US
dc.identifier.authorityCheung, ANY=rp00542en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros176675en_US
dc.publisher.placeUnited States-
dc.description.otherThe 101st Annual Meeting of the American Association for Cancer Research (AACR 2010), Washington D.C., 17-21 April 2010.-

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