Article: Effect of all-trans retinoic acid on tissue dynamics of choriocarcinoma cell lines: An organotypic model

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Title	Effect of all-trans retinoic acid on tissue dynamics of choriocarcinoma cell lines: An organotypic model
Authors	Chiu, PM1 Feng, HC1 Benbrook, DM2 Ngan, HYS1 Khoo, US1 Xue, WC1 Tsao, SW1 Chan, KW1 Cheung, ANY1
Issue Date	2006
Publisher	B M J Publishing Group. The Journal's web site is located at http://jcp.bmjjournals.com/
Citation	Journal Of Clinical Pathology, 2006, v. 59 n. 8, p. 845-850 [How to Cite?] DOI: http://dx.doi.org/10.1136/jcp.2005.025833
Abstract	Background: 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.
ISSN	0021-9746 2011 Impact Factor: 2.306 2011 SCImago Journal Rankings: 0.236
DOI	http://dx.doi.org/10.1136/jcp.2005.025833
ISI Accession Number ID	WOS:000239331100009
PubMed Central ID	PMC1860458
References	References in Scopus

DC Field	Value
dc.contributor.author	Chiu, PM
dc.contributor.author	Feng, HC
dc.contributor.author	Benbrook, DM
dc.contributor.author	Ngan, HYS
dc.contributor.author	Khoo, US
dc.contributor.author	Xue, WC
dc.contributor.author	Tsao, SW
dc.contributor.author	Chan, KW
dc.contributor.author	Cheung, ANY
dc.date.accessioned	2007-10-30T06:04:27Z
dc.date.available	2007-10-30T06:04:27Z
dc.date.issued	2006
dc.description.abstract	Background: 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.citation	Journal 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.doi	http://dx.doi.org/10.1136/jcp.2005.025833
dc.identifier.epage	850
dc.identifier.isi	WOS:000239331100009
dc.identifier.issn	0021-9746 2011 Impact Factor: 2.306 2011 SCImago Journal Rankings: 0.236
dc.identifier.issue	8
dc.identifier.openurl
dc.identifier.pmcid	PMC1860458
dc.identifier.pmid	16461808
dc.identifier.scopus	eid_2-s2.0-33747050675
dc.identifier.spage	845
dc.identifier.uri	http://hdl.handle.net/10722/44566
dc.identifier.volume	59
dc.language	eng
dc.publisher	B M J Publishing Group. The Journal's web site is located at http://jcp.bmjjournals.com/
dc.publisher.place	United Kingdom
dc.relation.ispartof	Journal of Clinical Pathology
dc.relation.references	References in Scopus
dc.rights	Journal of Clinical Pathology. Copyright © B M J Publishing Group.
dc.rights	Creative Commons: Attribution 3.0 Hong Kong License
dc.subject.mesh	Antineoplastic-Agents-pharmacology
dc.subject.mesh	Choriocarcinoma-pathology
dc.subject.mesh	Tretinoin-pharmacology
dc.title	Effect of all-trans retinoic acid on tissue dynamics of choriocarcinoma cell lines: An organotypic model
dc.type	Article

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Author Affiliations

The University of Hong Kong
University of Oklahoma Health Sciences Center