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Article: KRAB zinc finger protein ZNF382 is a proapoptotic tumor suppressor that represses multiple oncogenes and is commonly silenced in multiple carcinomas

TitleKRAB zinc finger protein ZNF382 is a proapoptotic tumor suppressor that represses multiple oncogenes and is commonly silenced in multiple carcinomas
Authors
Issue Date2010
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2010, v. 70 n. 16, p. 6516-6526 How to Cite?
AbstractZinc finger transcription factors are involved broadly in development and tumorigenesis. Here, we report that the little studied zinc finger transcription factor ZNF382 functions as a tumor suppressor in multiple carcinomas. Although broadly expressed in normal tissues, ZNF382 expression was attenuated in multiple carcinoma cell lines due to promoter CpG methylation. ZNF382 was also frequently methylated in multiple primary tumors (nasopharyngeal, esophageal, colon, gastric, and breast). Ectopic expression of ZNF382 in silenced tumor cells significantly inhibited their clonogenicity and proliferation and induced apoptosis. We further found that ZNF382 inhibited NF-κB and AP-1 signaling and downregulated the expression of multiple oncogenes including MYC, MITF, HMGA2, and CDK6, as well as the NF-κB upstream factors STAT3, STAT5B, ID1, and IKBKE, most likely through heterochromatin silencing. ZNF382 could suppress tumorigenesis through heterochromatin-mediated silencing, as ZNF382 was colocalized and interacted with heterochromatin protein HP1 and further changed the chromatin modifications of ZNF382 target oncogenes. Our data show that ZNF382 is a functional tumor suppressor frequently methylated in multiple carcinomas. ©2010 AACR.
Persistent Identifierhttp://hdl.handle.net/10722/129528
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
ISI Accession Number ID
Funding AgencyGrant Number
Chinese University of Hong Kong474407
Funding Information:

Hong Kong RGC grant 474407, Chinese University of Hong Kong Scheme C, and a Chinese University of Hong Kong direct grant.

References

 

DC FieldValueLanguage
dc.contributor.authorCheng, Yen_HK
dc.contributor.authorGeng, Hen_HK
dc.contributor.authorCheng, SHen_HK
dc.contributor.authorLiang, Pen_HK
dc.contributor.authorBai, Yen_HK
dc.contributor.authorLi, Jen_HK
dc.contributor.authorSrivastava, Gen_HK
dc.contributor.authorNg, MHLen_HK
dc.contributor.authorFukagawa, Ten_HK
dc.contributor.authorWu, Xen_HK
dc.contributor.authorChan, ATCen_HK
dc.contributor.authorTao, Qen_HK
dc.date.accessioned2010-12-23T08:38:28Z-
dc.date.available2010-12-23T08:38:28Z-
dc.date.issued2010en_HK
dc.identifier.citationCancer Research, 2010, v. 70 n. 16, p. 6516-6526en_HK
dc.identifier.issn0008-5472en_HK
dc.identifier.urihttp://hdl.handle.net/10722/129528-
dc.description.abstractZinc finger transcription factors are involved broadly in development and tumorigenesis. Here, we report that the little studied zinc finger transcription factor ZNF382 functions as a tumor suppressor in multiple carcinomas. Although broadly expressed in normal tissues, ZNF382 expression was attenuated in multiple carcinoma cell lines due to promoter CpG methylation. ZNF382 was also frequently methylated in multiple primary tumors (nasopharyngeal, esophageal, colon, gastric, and breast). Ectopic expression of ZNF382 in silenced tumor cells significantly inhibited their clonogenicity and proliferation and induced apoptosis. We further found that ZNF382 inhibited NF-κB and AP-1 signaling and downregulated the expression of multiple oncogenes including MYC, MITF, HMGA2, and CDK6, as well as the NF-κB upstream factors STAT3, STAT5B, ID1, and IKBKE, most likely through heterochromatin silencing. ZNF382 could suppress tumorigenesis through heterochromatin-mediated silencing, as ZNF382 was colocalized and interacted with heterochromatin protein HP1 and further changed the chromatin modifications of ZNF382 target oncogenes. Our data show that ZNF382 is a functional tumor suppressor frequently methylated in multiple carcinomas. ©2010 AACR.en_HK
dc.languageengen_US
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/en_HK
dc.relation.ispartofCancer Researchen_HK
dc.subject.meshAnimals-
dc.subject.meshDNA-Binding Proteins - biosynthesis - genetics-
dc.subject.meshGenes, Tumor Suppressor-
dc.subject.meshNeoplasms, Multiple Primary - genetics - metabolism - pathology-
dc.subject.meshTranscription Factors - biosynthesis - genetics-
dc.titleKRAB zinc finger protein ZNF382 is a proapoptotic tumor suppressor that represses multiple oncogenes and is commonly silenced in multiple carcinomasen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0008-5472&volume=70&issue=16&spage=6516&epage=6526&date=2010&atitle=KRAB+zinc+finger+protein+ZNF382+is+a+proapoptotic+tumor+suppressor+that+represses+multiple+oncogenes+and+is+commonly+silenced+in+multiple+carcinomas-
dc.identifier.emailSrivastava, G:gopesh@pathology.hku.hken_HK
dc.identifier.authoritySrivastava, G=rp00365en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1158/0008-5472.CAN-09-4566en_HK
dc.identifier.pmid20682794-
dc.identifier.scopuseid_2-s2.0-77955728660en_HK
dc.identifier.hkuros176922en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77955728660&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume70en_HK
dc.identifier.issue16en_HK
dc.identifier.spage6516en_HK
dc.identifier.epage6526en_HK
dc.identifier.isiWOS:000280887000014-
dc.publisher.placeUnited Statesen_HK

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