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Article: The candidate tumor suppressor gene BLU, located at the commonly deleted region 3p21.3, is an E2F-regulated, stress-responsive gene and inactivated by both epigenetic and genetic mechanisms in nasopharyngeal carcinoma

TitleThe candidate tumor suppressor gene BLU, located at the commonly deleted region 3p21.3, is an E2F-regulated, stress-responsive gene and inactivated by both epigenetic and genetic mechanisms in nasopharyngeal carcinoma
Authors
Keywords3p21
BLU
Heat shock
Methylation
NPC
RASSF1A
Issue Date2004
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2004, v. 23 n. 27, p. 4793-4806 How to Cite?
AbstractLoss of heterozygosity at 3p21 is common in various cancers including nasopharyngeal carcinoma (NPC). BLU is one of the candidate tumor suppressor genes (TSGs) in this region. Ectopic expression of BLU results in the inhibition of colony formation of cancer cells, suggesting that BLU is a tumor suppressor. We have identified a functional BLU promoter and found that it can be activated by environmental stresses such as heat shock, and is regulated by E2F. The promoter and first exon are located within a CpG island. BLU is highly expressed in testis and normal upper respiratory tract tissues including nasopharynx. However, in all seven NPC cell lines examined, BLU expression was downregulated and inversely correlated with promoter hypermethylation. Biallelic epigenetic inactivation of BLU was also observed in three cell lines. Hypermethylation was further detected in 19/29 (66%) of primary NPC tumors, but not in normal nasopharyngeal tissues. Treatment of NPC cell lines with 5-aza-2′- deoxycytidine activated BLU expression along with promoter demethylation. Although hypermethylation of RASSF1A, another TSG located immediately downstream of BLU, was detected in 20/27 (74%) of NPC tumors, no correlation between the hypermethylation of these two TSGs was observed (P = 0.6334). In addition to methylation, homozygous deletion of BLU was found in 7/29 (24%) of tumors. Therefore, BLU is a stress-responsive gene, being disrupted in 83% (24/29) of NPC tumors by either epigenetic or genetic mechanisms. Our data are consistent with the interpretation that BLU is a TSG for NPC.
Persistent Identifierhttp://hdl.handle.net/10722/148440
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorQiu, GHen_HK
dc.contributor.authorTan, LKSen_HK
dc.contributor.authorLoh, KSen_HK
dc.contributor.authorLim, CYen_HK
dc.contributor.authorSrivastava, Gen_HK
dc.contributor.authorTsai, STen_HK
dc.contributor.authorTsao, SWen_HK
dc.contributor.authorTao, Qen_HK
dc.date.accessioned2012-05-29T06:12:59Z-
dc.date.available2012-05-29T06:12:59Z-
dc.date.issued2004en_HK
dc.identifier.citationOncogene, 2004, v. 23 n. 27, p. 4793-4806en_HK
dc.identifier.issn0950-9232en_HK
dc.identifier.urihttp://hdl.handle.net/10722/148440-
dc.description.abstractLoss of heterozygosity at 3p21 is common in various cancers including nasopharyngeal carcinoma (NPC). BLU is one of the candidate tumor suppressor genes (TSGs) in this region. Ectopic expression of BLU results in the inhibition of colony formation of cancer cells, suggesting that BLU is a tumor suppressor. We have identified a functional BLU promoter and found that it can be activated by environmental stresses such as heat shock, and is regulated by E2F. The promoter and first exon are located within a CpG island. BLU is highly expressed in testis and normal upper respiratory tract tissues including nasopharynx. However, in all seven NPC cell lines examined, BLU expression was downregulated and inversely correlated with promoter hypermethylation. Biallelic epigenetic inactivation of BLU was also observed in three cell lines. Hypermethylation was further detected in 19/29 (66%) of primary NPC tumors, but not in normal nasopharyngeal tissues. Treatment of NPC cell lines with 5-aza-2′- deoxycytidine activated BLU expression along with promoter demethylation. Although hypermethylation of RASSF1A, another TSG located immediately downstream of BLU, was detected in 20/27 (74%) of NPC tumors, no correlation between the hypermethylation of these two TSGs was observed (P = 0.6334). In addition to methylation, homozygous deletion of BLU was found in 7/29 (24%) of tumors. Therefore, BLU is a stress-responsive gene, being disrupted in 83% (24/29) of NPC tumors by either epigenetic or genetic mechanisms. Our data are consistent with the interpretation that BLU is a TSG for NPC.en_HK
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/oncen_HK
dc.relation.ispartofOncogeneen_HK
dc.subject3p21en_HK
dc.subjectBLUen_HK
dc.subjectHeat shocken_HK
dc.subjectMethylationen_HK
dc.subjectNPCen_HK
dc.subjectRASSF1Aen_HK
dc.subject.meshAllelesen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAzacitidine - Analogs & Derivatives - Pharmacologyen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshCarcinoma - Genetics - Pathologyen_US
dc.subject.meshCell Lineen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshCell Transformation, Viralen_US
dc.subject.meshChromosomes, Human, Pair 3en_US
dc.subject.meshCpg Islandsen_US
dc.subject.meshDna Methylationen_US
dc.subject.meshEnzyme Inhibitors - Pharmacologyen_US
dc.subject.meshEpigenesis, Geneticen_US
dc.subject.meshGene Deletionen_US
dc.subject.meshGene Expression Regulation, Neoplasticen_US
dc.subject.meshGene Silencingen_US
dc.subject.meshGenes, Tumor Suppressoren_US
dc.subject.meshHumansen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Nudeen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshNasopharyngeal Neoplasms - Genetics - Pathologyen_US
dc.subject.meshPromoter Regions, Geneticen_US
dc.subject.meshProtein Bindingen_US
dc.subject.meshStress, Physiological - Geneticsen_US
dc.subject.meshTumor Suppressor Proteins - Geneticsen_US
dc.titleThe candidate tumor suppressor gene BLU, located at the commonly deleted region 3p21.3, is an E2F-regulated, stress-responsive gene and inactivated by both epigenetic and genetic mechanisms in nasopharyngeal carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.emailSrivastava, G:gopesh@pathology.hku.hken_HK
dc.identifier.emailTsao, SW:gswtsao@hkucc.hku.hken_HK
dc.identifier.authoritySrivastava, G=rp00365en_HK
dc.identifier.authorityTsao, SW=rp00399en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/sj.onc.1207632en_HK
dc.identifier.pmid15122337-
dc.identifier.scopuseid_2-s2.0-2942737278en_HK
dc.identifier.hkuros87419-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-2942737278&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume23en_HK
dc.identifier.issue27en_HK
dc.identifier.spage4793en_HK
dc.identifier.epage4806en_HK
dc.identifier.isiWOS:000221799200015-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridQiu, GH=7103292122en_HK
dc.identifier.scopusauthoridTan, LKS=8059320500en_HK
dc.identifier.scopusauthoridLoh, KS=7103139980en_HK
dc.identifier.scopusauthoridLim, CY=7403654102en_HK
dc.identifier.scopusauthoridSrivastava, G=7202242238en_HK
dc.identifier.scopusauthoridTsai, ST=7403478735en_HK
dc.identifier.scopusauthoridTsao, SW=7102813116en_HK
dc.identifier.scopusauthoridTao, Q=7102578359en_HK

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