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Article: Effect of all-trans retinoic acid on tissue dynamics of choriocarcinoma cell lines: An organotypic model
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TitleEffect of all-trans retinoic acid on tissue dynamics of choriocarcinoma cell lines: An organotypic model
 
AuthorsChiu, PM1
Feng, HC1
Benbrook, DM2
Ngan, HYS1
Khoo, US1
Xue, WC1
Tsao, SW1
Chan, KW1
Cheung, ANY1
 
Issue Date2006
 
PublisherB M J Publishing Group. The Journal's web site is located at http://jcp.bmjjournals.com/
 
CitationJournal Of Clinical Pathology, 2006, v. 59 n. 8, p. 845-850 [How to Cite?]
DOI: http://dx.doi.org/10.1136/jcp.2005.025833
 
AbstractBackground: All-trans retinoic acid (ATRA) is a natural vitamin A derivative that has a profound effect on the regulation of cell growth, differentiation and death. Aim: To investigate the tissue dynamic and cellular invasion effects of ATRA in choriocarcinoma (CCA), an aggressive trophoblastic tumour, by using a three-dimensional organotypic culture model system and cell invasion assay, respectively. Methods: An organotypic culture model of two CCA cell lines, JAR and JEG, was established. The effects of 1 μM ATRA on proliferation, differentiation and apoptosis on this CCA model were assessed by morphological assessment of the mitotic and apoptotic figures as well as by Ki-67 and caspase-related M30 cytoDeath antibody immunohistochemistry and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay. The effect of ATRA on p53 and its regulated protein product, WAF1/Cip1, was also evaluated with DO7 and p21 WAF1 antibodies, respectively. Moreover, the effect of ATRA on cellular (CCA) invasion was also investigated with Cell Invasion Kit on the JEG cell line. Results: ATRA was found to induce marked apoptosis in organotypic cultures of both cell lines, as evidenced by increased M30-positive cells (p<0.0001) and increased TUNEL-positive cells (p<0.0001) in treated cultures; to decrease proliferation, as evidenced by decreased Ki-67-positive cells (p<0.0001); and to decrease p53-DO7 immunoreactivity (p<0.0001) and increase p21 WAF1 (p<0.0001) immunoreactivity. 1.5 μM ATRA was found to effectively inhibit JEG cell invasion in the cell invasion assay. Conclusion: ATRA treatment was found to inhibit invasion and proliferation and enhance apoptosis, probably by the activation of caspases and induction of differentiation. ATRA and synthetic retinoids may be alternative agents for the treatment of CCA.
 
ISSN0021-9746
2012 Impact Factor: 2.439
2012 SCImago Journal Rankings: 0.980
 
DOIhttp://dx.doi.org/10.1136/jcp.2005.025833
 
PubMed Central IDPMC1860458
 
ISI Accession Number IDWOS:000239331100009
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorChiu, PM
 
dc.contributor.authorFeng, HC
 
dc.contributor.authorBenbrook, DM
 
dc.contributor.authorNgan, HYS
 
dc.contributor.authorKhoo, US
 
dc.contributor.authorXue, WC
 
dc.contributor.authorTsao, SW
 
dc.contributor.authorChan, KW
 
dc.contributor.authorCheung, ANY
 
dc.date.accessioned2007-10-30T06:04:27Z
 
dc.date.available2007-10-30T06:04:27Z
 
dc.date.issued2006
 
dc.description.abstractBackground: All-trans retinoic acid (ATRA) is a natural vitamin A derivative that has a profound effect on the regulation of cell growth, differentiation and death. Aim: To investigate the tissue dynamic and cellular invasion effects of ATRA in choriocarcinoma (CCA), an aggressive trophoblastic tumour, by using a three-dimensional organotypic culture model system and cell invasion assay, respectively. Methods: An organotypic culture model of two CCA cell lines, JAR and JEG, was established. The effects of 1 μM ATRA on proliferation, differentiation and apoptosis on this CCA model were assessed by morphological assessment of the mitotic and apoptotic figures as well as by Ki-67 and caspase-related M30 cytoDeath antibody immunohistochemistry and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay. The effect of ATRA on p53 and its regulated protein product, WAF1/Cip1, was also evaluated with DO7 and p21 WAF1 antibodies, respectively. Moreover, the effect of ATRA on cellular (CCA) invasion was also investigated with Cell Invasion Kit on the JEG cell line. Results: ATRA was found to induce marked apoptosis in organotypic cultures of both cell lines, as evidenced by increased M30-positive cells (p<0.0001) and increased TUNEL-positive cells (p<0.0001) in treated cultures; to decrease proliferation, as evidenced by decreased Ki-67-positive cells (p<0.0001); and to decrease p53-DO7 immunoreactivity (p<0.0001) and increase p21 WAF1 (p<0.0001) immunoreactivity. 1.5 μM ATRA was found to effectively inhibit JEG cell invasion in the cell invasion assay. Conclusion: ATRA treatment was found to inhibit invasion and proliferation and enhance apoptosis, probably by the activation of caspases and induction of differentiation. ATRA and synthetic retinoids may be alternative agents for the treatment of CCA.
 
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dc.identifier.citationJournal Of Clinical Pathology, 2006, v. 59 n. 8, p. 845-850 [How to Cite?]
DOI: http://dx.doi.org/10.1136/jcp.2005.025833
 
dc.identifier.doihttp://dx.doi.org/10.1136/jcp.2005.025833
 
dc.identifier.epage850
 
dc.identifier.isiWOS:000239331100009
 
dc.identifier.issn0021-9746
2012 Impact Factor: 2.439
2012 SCImago Journal Rankings: 0.980
 
dc.identifier.issue8
 
dc.identifier.openurl
 
dc.identifier.pmcidPMC1860458
 
dc.identifier.pmid16461808
 
dc.identifier.scopuseid_2-s2.0-33747050675
 
dc.identifier.spage845
 
dc.identifier.urihttp://hdl.handle.net/10722/44566
 
dc.identifier.volume59
 
dc.languageeng
 
dc.publisherB M J Publishing Group. The Journal's web site is located at http://jcp.bmjjournals.com/
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofJournal of Clinical Pathology
 
dc.relation.referencesReferences in Scopus
 
dc.rightsJournal of Clinical Pathology. Copyright © B M J Publishing Group.
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.subject.meshAntineoplastic-Agents-pharmacology
 
dc.subject.meshChoriocarcinoma-pathology
 
dc.subject.meshTretinoin-pharmacology
 
dc.titleEffect of all-trans retinoic acid on tissue dynamics of choriocarcinoma cell lines: An organotypic model
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong
  2. University of Oklahoma Health Sciences Center