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Article: The stress-responsive gene GADD45G is a functional tumor suppressor, with its response to environmental stresses frequently disrupted epigenetically in multiple tumors

TitleThe stress-responsive gene GADD45G is a functional tumor suppressor, with its response to environmental stresses frequently disrupted epigenetically in multiple tumors
Authors
Issue Date2005
PublisherAmerican Association for Cancer Research.
Citation
Clinical Cancer Research, 2005, v. 11 n. 18, p. 6442-6449 How to Cite?
AbstractThe CpG island of GADD45G was identified as a target sequence during the identification of hypermethylated genes using methylation-sensitive representational difference analysis combined with 5-aza-2′-deoxycytidine demethylation. Located at the commonly deleted region 9q22, GADD45G is a member of the DNA damage-inducible gene family. In response to stress shock, GADD45G inhibits cell growth and induces apoptosis. Same as other GADD45 members, GADD45G is ubiquitously expressed in all normal adult and fetal tissues. However, its transcrip-tional silencing or down-regulation and promoter hypermethylation were frequently detected in tumor cell lines, including 11 of 13 (85%) non-Hodgkin's lymphoma, 3 of 6 (50%) Hodgkin's lymphoma, 8 of 11 (73%) nasopharyngeal carcinoma, 2 of 4 (50%) cervical carcinoma, 5 of 17 (29%) esophageal carcinoma, and 2 of 5 (40%) lung carcinoma and other cell lines but not in any immortalized normal epithelial cell line, normal tissue, or peripheral blood mononuclear cells. The silencing of GADD45G could be reversed by 5-aza-2′-deoxycytidine or genetic double knockout of DNMT1 and DNMT3B, indicating a direct epigenetic mechanism. Aberrant methylation was further frequently detected in primary lymphomas although less frequently in primary carcinomas. Only one single sequence change in the coding region was detected in 1 of 25 cell lines examined, indicating that genetic inactivation of GADD45G is very rare. GADD45G could be induced by heat shock or UV irradiation in unmethylated cell lines; however, this stress response was abolished when its promoter becomes hypermethylated. Ectopic expression of GADD45G strongly suppressed tumor cell growth and colony formation in silenced cell lines. These results show that GADD45G can act as a functional new-age tumor suppressor but being frequently inactivated epigenetically in multiple tumors. © 2005 American Association for Cancer Research.
Persistent Identifierhttp://hdl.handle.net/10722/88673
ISSN
2015 Impact Factor: 8.738
2015 SCImago Journal Rankings: 5.314
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYing, Jen_HK
dc.contributor.authorSrivastava, Gen_HK
dc.contributor.authorHsieh, WSen_HK
dc.contributor.authorGao, Zen_HK
dc.contributor.authorMurray, Pen_HK
dc.contributor.authorLiao, SKen_HK
dc.contributor.authorAmbinder, Ren_HK
dc.contributor.authorTao, Qen_HK
dc.date.accessioned2010-09-06T09:46:28Z-
dc.date.available2010-09-06T09:46:28Z-
dc.date.issued2005en_HK
dc.identifier.citationClinical Cancer Research, 2005, v. 11 n. 18, p. 6442-6449en_HK
dc.identifier.issn1078-0432en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88673-
dc.description.abstractThe CpG island of GADD45G was identified as a target sequence during the identification of hypermethylated genes using methylation-sensitive representational difference analysis combined with 5-aza-2′-deoxycytidine demethylation. Located at the commonly deleted region 9q22, GADD45G is a member of the DNA damage-inducible gene family. In response to stress shock, GADD45G inhibits cell growth and induces apoptosis. Same as other GADD45 members, GADD45G is ubiquitously expressed in all normal adult and fetal tissues. However, its transcrip-tional silencing or down-regulation and promoter hypermethylation were frequently detected in tumor cell lines, including 11 of 13 (85%) non-Hodgkin's lymphoma, 3 of 6 (50%) Hodgkin's lymphoma, 8 of 11 (73%) nasopharyngeal carcinoma, 2 of 4 (50%) cervical carcinoma, 5 of 17 (29%) esophageal carcinoma, and 2 of 5 (40%) lung carcinoma and other cell lines but not in any immortalized normal epithelial cell line, normal tissue, or peripheral blood mononuclear cells. The silencing of GADD45G could be reversed by 5-aza-2′-deoxycytidine or genetic double knockout of DNMT1 and DNMT3B, indicating a direct epigenetic mechanism. Aberrant methylation was further frequently detected in primary lymphomas although less frequently in primary carcinomas. Only one single sequence change in the coding region was detected in 1 of 25 cell lines examined, indicating that genetic inactivation of GADD45G is very rare. GADD45G could be induced by heat shock or UV irradiation in unmethylated cell lines; however, this stress response was abolished when its promoter becomes hypermethylated. Ectopic expression of GADD45G strongly suppressed tumor cell growth and colony formation in silenced cell lines. These results show that GADD45G can act as a functional new-age tumor suppressor but being frequently inactivated epigenetically in multiple tumors. © 2005 American Association for Cancer Research.en_HK
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research.en_HK
dc.relation.ispartofClinical Cancer Researchen_HK
dc.subject.meshAntigens, Differentiation - geneticsen_HK
dc.subject.meshAntimetabolites, Antineoplastic - pharmacologyen_HK
dc.subject.meshAzacitidine - analogs & derivatives - pharmacologyen_HK
dc.subject.meshBase Sequenceen_HK
dc.subject.meshCell Cycle Proteins - geneticsen_HK
dc.subject.meshCell Lineen_HK
dc.subject.meshCell Line, Tumoren_HK
dc.subject.meshCell Proliferationen_HK
dc.subject.meshCpG Islands - geneticsen_HK
dc.subject.meshDNA Methylation - drug effectsen_HK
dc.subject.meshDNA Modification Methylases - antagonists & inhibitorsen_HK
dc.subject.meshGene Expression Regulation, Neoplastic - drug effectsen_HK
dc.subject.meshHL-60 Cellsen_HK
dc.subject.meshHT29 Cellsen_HK
dc.subject.meshHeLa Cellsen_HK
dc.subject.meshHot Temperatureen_HK
dc.subject.meshHumansen_HK
dc.subject.meshIntracellular Signaling Peptides and Proteins - geneticsen_HK
dc.subject.meshK562 Cellsen_HK
dc.subject.meshMutationen_HK
dc.subject.meshNeoplasms - drug therapy - genetics - pathologyen_HK
dc.subject.meshNuclear Proteins - geneticsen_HK
dc.subject.meshPromoter Regions, Genetic - geneticsen_HK
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_HK
dc.subject.meshTumor Suppressor Proteins - geneticsen_HK
dc.titleThe stress-responsive gene GADD45G is a functional tumor suppressor, with its response to environmental stresses frequently disrupted epigenetically in multiple tumorsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1078-0432&volume=11&issue=18&spage=6442&epage=6449&date=2005&atitle=The+stress-responsive+gene+GADD45G+is+a+functional+tumor+suppressor,+with+its+response+to+environmental+stresses+frequently+disrupted+epigenetically+in+multiple+tumorsen_HK
dc.identifier.emailSrivastava, G:gopesh@pathology.hku.hken_HK
dc.identifier.authoritySrivastava, G=rp00365en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1158/1078-0432.CCR-05-0267en_HK
dc.identifier.pmid16166418-
dc.identifier.scopuseid_2-s2.0-25144510121en_HK
dc.identifier.hkuros105063en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-25144510121&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume11en_HK
dc.identifier.issue18en_HK
dc.identifier.spage6442en_HK
dc.identifier.epage6449en_HK
dc.identifier.isiWOS:000232016100005-
dc.publisher.placeUnited Statesen_HK
dc.identifier.citeulike921451-

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