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Conference Paper: PDCD4 as a prognostic factor and a modulator of cell proliferation, migration and invasion in ovarian cancer

TitlePDCD4 as a prognostic factor and a modulator of cell proliferation, migration and invasion in ovarian cancer
Authors
Issue Date2010
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://www.aacrmeetingabstracts.org/
Citation
The 101st Annual Meeting of the American Association for Cancer Research (AACR 2010), Washington, DC., 17-21 April 2010. In AACR Meeting Abstracts, 2010 How to Cite?
AbstractProgrammed cell death 4 (Pdcd4), a novel gene and originally identified as the neoplastic transformation inhibitor, is down regulated in human colon, breast and lung cancer cells and considered as a diagnostic and prognostic marker in lung cancer. It has been shown to have tumor suppressor properties such as inhibition of cell invasion and proliferation, as well as induction of apoptosis. However, those properties of Pdcd4 are tissue specific. The mechanisms of function of Pdcd4 are largely unknown and its function and modulation in ovarian cancer is still elusive. The objectives of our present study are firstly to investigate the expression of Pdcd4 in normal and malignant ovarian tissues and the role of Pdcd4 in ovarian carcinogenesis; and secondly, to study the function of Pdcd4 in the regulation of cell proliferation, migration and invasion and modulation of Pdcd4 in ovarian cancer. Using both western blot and real-time quantitative PCR analyses, we demonstrated that Pdcd4 expression was continuously down-regulated in the sequence of normal-borderline-malignant ovarian tissue samples. Higher Pdcd4 expression was found to be associated with longer disease-free survival (p=0.037). Using immunohistochemical staining approach, we found the subcellular localization of Pdcd4 differed in the way that, normal ovarian tissues showed distinctive nuclear localization while malignant ovarian tissues showed mainly cytoplasmic staining. To further explore the function of Pdcd4 in ovarian cancer cells, we developed Pdcd4 over-expression stable clones in ovarian cancer cell lines. Our in vitro studies demonstrated that ectopic Pdcd4 expression significantly inhibited ovarian cancer cell proliferation by inducing cell cycle arrest at G0/G1 stage and the upregulation of cell cycle regulators p27 and p21. The induction of p21 by Pdcd4 was not mediated through p53. Using wound healing, transwell migration and invasion assay, we demonstrated Pdcd4 significantly inhibited ovarian cancer cell migration and invasion. In conclusion, loss of Pdcd4 was a common abnormality at molecular level in ovarian cancer and it might be a potential prognostic factor in ovarian cancer patients. In addition, our results also provided first evidence for the tumor suppressor properties of Pdcd4 in inhibition of cell proliferation by inducing cell cycle arrest and modulating cell cycle regulators, as well as inhibition of cell migration and invasion in ovarian cancer cells.
DescriptionPoster Session 7 - Novel Tumor Suppressor Genes 2: abstract no. 5006
Persistent Identifierhttp://hdl.handle.net/10722/130049
ISSN

 

DC FieldValueLanguage
dc.contributor.authorWei, Nen_US
dc.contributor.authorLiu, SSen_US
dc.contributor.authorLeung, THLen_US
dc.contributor.authorTam, KFen_US
dc.contributor.authorLiao, XYen_US
dc.contributor.authorCheung, ANY-
dc.contributor.authorChan, KKL-
dc.contributor.authorNgan, HYS-
dc.date.accessioned2010-12-23T08:46:05Z-
dc.date.available2010-12-23T08:46:05Z-
dc.date.issued2010en_US
dc.identifier.citationThe 101st Annual Meeting of the American Association for Cancer Research (AACR 2010), Washington, DC., 17-21 April 2010. In AACR Meeting Abstracts, 2010en_US
dc.identifier.issn1948-3279-
dc.identifier.urihttp://hdl.handle.net/10722/130049-
dc.descriptionPoster Session 7 - Novel Tumor Suppressor Genes 2: abstract no. 5006-
dc.description.abstractProgrammed cell death 4 (Pdcd4), a novel gene and originally identified as the neoplastic transformation inhibitor, is down regulated in human colon, breast and lung cancer cells and considered as a diagnostic and prognostic marker in lung cancer. It has been shown to have tumor suppressor properties such as inhibition of cell invasion and proliferation, as well as induction of apoptosis. However, those properties of Pdcd4 are tissue specific. The mechanisms of function of Pdcd4 are largely unknown and its function and modulation in ovarian cancer is still elusive. The objectives of our present study are firstly to investigate the expression of Pdcd4 in normal and malignant ovarian tissues and the role of Pdcd4 in ovarian carcinogenesis; and secondly, to study the function of Pdcd4 in the regulation of cell proliferation, migration and invasion and modulation of Pdcd4 in ovarian cancer. Using both western blot and real-time quantitative PCR analyses, we demonstrated that Pdcd4 expression was continuously down-regulated in the sequence of normal-borderline-malignant ovarian tissue samples. Higher Pdcd4 expression was found to be associated with longer disease-free survival (p=0.037). Using immunohistochemical staining approach, we found the subcellular localization of Pdcd4 differed in the way that, normal ovarian tissues showed distinctive nuclear localization while malignant ovarian tissues showed mainly cytoplasmic staining. To further explore the function of Pdcd4 in ovarian cancer cells, we developed Pdcd4 over-expression stable clones in ovarian cancer cell lines. Our in vitro studies demonstrated that ectopic Pdcd4 expression significantly inhibited ovarian cancer cell proliferation by inducing cell cycle arrest at G0/G1 stage and the upregulation of cell cycle regulators p27 and p21. The induction of p21 by Pdcd4 was not mediated through p53. Using wound healing, transwell migration and invasion assay, we demonstrated Pdcd4 significantly inhibited ovarian cancer cell migration and invasion. In conclusion, loss of Pdcd4 was a common abnormality at molecular level in ovarian cancer and it might be a potential prognostic factor in ovarian cancer patients. In addition, our results also provided first evidence for the tumor suppressor properties of Pdcd4 in inhibition of cell proliferation by inducing cell cycle arrest and modulating cell cycle regulators, as well as inhibition of cell migration and invasion in ovarian cancer cells.-
dc.languageengen_US
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://www.aacrmeetingabstracts.org/-
dc.relation.ispartofAACR Meeting Abstracts-
dc.titlePDCD4 as a prognostic factor and a modulator of cell proliferation, migration and invasion in ovarian canceren_US
dc.typeConference_Paperen_US
dc.identifier.emailLiu, SS: stephasl@HKUCC.hku.hken_US
dc.identifier.emailLeung, THL: thomas@pathology.hku.hken_US
dc.identifier.emailTam, KF: tamkf@hkucc.hku.hken_US
dc.identifier.emailCheung, ANY: anycheun@hkucc.hku.hken_US
dc.identifier.emailChan, KKL: karenchan@pobox.com-
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hk-
dc.identifier.hkuros177268en_US
dc.description.otherThe 101st Annual Meeting of the American Association for Cancer Research (AACR), Washington, DC., 17-21 April 2010. In AACR Meeting Abstracts, 2010-

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