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postgraduate thesis: The effects of 5-aza-2'-deoxycytidine and trichostatin A on FBI-1 gene expression in choriocarcinoma cell lines

TitleThe effects of 5-aza-2'-deoxycytidine and trichostatin A on FBI-1 gene expression in choriocarcinoma cell lines
Authors
Issue Date2014
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Chan, S. C. [陳思慧]. (2014). The effects of 5-aza-2'-deoxycytidine and trichostatin A on FBI-1 gene expression in choriocarcinoma cell lines. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5318892
AbstractChoriocarcinoma is a rare, aggressive malignant epithelial tumor that can be arisen from gestational or non-gestational origins. Gestational choriocarcinoma is found primarily in uterus and is a malignant form of gestational trophoblastic disease. The tumor can easily metastasize to other organs through blood vessels and fatal outcome would be resulted if untreated. Nevertheless, the underlying pathogenesis is not fully explored and understood. FBI-1 is a proto-oncogene and acts as a transcriptional repressor for many cellular processes. Overexpression of FBI-1 was observed in various types of cancers including gestational choriocarcinoma. However, little is known on the mechanisms of regulation of FBI-1 gene expression. In this study, by treating with two epigenetic remodeling drugs, 5-aza-2’-deoxycytidine (5-aza-dc) and trichostatin A (TSA), mRNA and protein expressions of FBI-1 were investigated in gestational choriocarcinoma cell lines, JEG-3 and JAR by using quantitative real-time PCR and western blotting. The morphological changes and cell survival after treatment of 5-aza-dc or TSA on JEG-3 and JAR cell lines was also assessed, the latterby3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay. This study demonstrated that FBI-1 protein was overexpressed in JEG-3 and JAR cells compared to normal trophoblastic cell line. Moreover, FBI-1 expressions in JEG-3 and JAR cells were down-regulated in TSA treatment but remained unchanged in 5-aza-dc treatment. It implies that HDAC inhibitor is able to regulate the expression of FBI-1 gene. After treatment with TSA at 0.3Mor 0.6M, both JEG-3 and JAR cells demonstrated significant morphological changes when comparing with the untreated controls, becoming elongated, distorted, rounder and smalleras well as increasingly detached and floating suggestive of cell death. Such changes were not significantly observed in 5-aza-dctreated cells. In addition, more significant reduction in cell survival as assessed by MTT assay was found in TSA than in 5-aza-dc treatment. This may be related to the decrease inFBI-1 expression after TSA treatment. In summary, histone modification may play a role in the regulation of FBI-1 expression in gestational choriocarcinoma cells affecting the cell survival.
DegreeMaster of Medical Sciences
SubjectTrophoblastic tumors
Dept/ProgramPathology
Persistent Identifierhttp://hdl.handle.net/10722/206561

 

DC FieldValueLanguage
dc.contributor.authorChan, Sze-wai, Cicilia-
dc.contributor.author陳思慧-
dc.date.accessioned2014-11-19T23:15:29Z-
dc.date.available2014-11-19T23:15:29Z-
dc.date.issued2014-
dc.identifier.citationChan, S. C. [陳思慧]. (2014). The effects of 5-aza-2'-deoxycytidine and trichostatin A on FBI-1 gene expression in choriocarcinoma cell lines. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5318892-
dc.identifier.urihttp://hdl.handle.net/10722/206561-
dc.description.abstractChoriocarcinoma is a rare, aggressive malignant epithelial tumor that can be arisen from gestational or non-gestational origins. Gestational choriocarcinoma is found primarily in uterus and is a malignant form of gestational trophoblastic disease. The tumor can easily metastasize to other organs through blood vessels and fatal outcome would be resulted if untreated. Nevertheless, the underlying pathogenesis is not fully explored and understood. FBI-1 is a proto-oncogene and acts as a transcriptional repressor for many cellular processes. Overexpression of FBI-1 was observed in various types of cancers including gestational choriocarcinoma. However, little is known on the mechanisms of regulation of FBI-1 gene expression. In this study, by treating with two epigenetic remodeling drugs, 5-aza-2’-deoxycytidine (5-aza-dc) and trichostatin A (TSA), mRNA and protein expressions of FBI-1 were investigated in gestational choriocarcinoma cell lines, JEG-3 and JAR by using quantitative real-time PCR and western blotting. The morphological changes and cell survival after treatment of 5-aza-dc or TSA on JEG-3 and JAR cell lines was also assessed, the latterby3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay. This study demonstrated that FBI-1 protein was overexpressed in JEG-3 and JAR cells compared to normal trophoblastic cell line. Moreover, FBI-1 expressions in JEG-3 and JAR cells were down-regulated in TSA treatment but remained unchanged in 5-aza-dc treatment. It implies that HDAC inhibitor is able to regulate the expression of FBI-1 gene. After treatment with TSA at 0.3Mor 0.6M, both JEG-3 and JAR cells demonstrated significant morphological changes when comparing with the untreated controls, becoming elongated, distorted, rounder and smalleras well as increasingly detached and floating suggestive of cell death. Such changes were not significantly observed in 5-aza-dctreated cells. In addition, more significant reduction in cell survival as assessed by MTT assay was found in TSA than in 5-aza-dc treatment. This may be related to the decrease inFBI-1 expression after TSA treatment. In summary, histone modification may play a role in the regulation of FBI-1 expression in gestational choriocarcinoma cells affecting the cell survival.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.subject.lcshTrophoblastic tumors-
dc.titleThe effects of 5-aza-2'-deoxycytidine and trichostatin A on FBI-1 gene expression in choriocarcinoma cell lines-
dc.typePG_Thesis-
dc.identifier.hkulb5318892-
dc.description.thesisnameMaster of Medical Sciences-
dc.description.thesislevelMaster-
dc.description.thesisdisciplinePathology-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b5318892-

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