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Article: Vitamin D3 upregulated protein 1 suppresses TNF-α–induced NF-κB activation in hepatocarcinogenesis

TitleVitamin D3 upregulated protein 1 suppresses TNF-α–induced NF-κB activation in hepatocarcinogenesis
Authors
Issue Date2010
PublisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.org
Citation
Journal of Immunology, 2010, v. 185 n. 7, p. 3980-3989 How to Cite?
AbstractVitamin D(3) upregulated protein 1 (VDUP1) is a candidate tumor suppressor, the expression of which is dramatically reduced in various tumor tissues. In this study, we found that VDUP1 expression is suppressed during human hepatic carcinogenesis, and mice lacking VDUP1 are much more susceptible to diethylnitrosamine-induced hepatocarcinogenesis compared with wild type mice. VDUP1-deficient tumors proliferated significantly more than wild type tumors and had corresponding changes in the expression of key cell cycle regulatory proteins. In addition, the hepatomitogen-induced response was associated with a considerable increase in the release of TNF-alpha and subsequent enhancement of NF-kappaB activation in VDUP1-deficient mice. When cells were treated with TNF-alpha, the VDUP1 level was markedly reduced, concomitant with elevated NF-kappaB activation. Furthermore, the overexpression of VDUP1 resulted in the robust suppression of TNF-alpha-activated NF-kappaB activity via association with HDAC1 and HDAC3. These results indicate that VDUP1 negatively regulates hepatocarcinogenesis by suppressing TNF-alpha-induced NF-kappaB activation.
Persistent Identifierhttp://hdl.handle.net/10722/129382
ISSN
2015 Impact Factor: 4.985
2015 SCImago Journal Rankings: 3.549
ISI Accession Number ID
Funding AgencyGrant Number
Global research lab
New Drug Target Discovery ProjectM10848000352-08N4800-35210
Ministry of Education, Science and Technology, Republic of South Korea
Funding Information:

This work was supported in part by grants from the global research lab project and the New Drug Target Discovery Project (M10848000352-08N4800-35210), the Ministry of Education, Science and Technology, Republic of South Korea.

 

DC FieldValueLanguage
dc.contributor.authorKwon, HJen_US
dc.contributor.authorWon, YSen_US
dc.contributor.authorSuh, HWen_US
dc.contributor.authorJeon, JHen_US
dc.contributor.authorShao, Yen_US
dc.contributor.authorYoon, SRen_US
dc.contributor.authorChung, JWen_US
dc.contributor.authorKim, TDen_US
dc.contributor.authorKim, HMen_US
dc.contributor.authorNam, KH-
dc.contributor.authorYoon, WK-
dc.contributor.authorKim, DG-
dc.contributor.authorKim, JH-
dc.contributor.authorKim, YS-
dc.contributor.authorKim, DY-
dc.contributor.authorKim, HC-
dc.contributor.authorChoi, I-
dc.date.accessioned2010-12-23T08:36:35Z-
dc.date.available2010-12-23T08:36:35Z-
dc.date.issued2010en_US
dc.identifier.citationJournal of Immunology, 2010, v. 185 n. 7, p. 3980-3989en_US
dc.identifier.issn0022-1767en_US
dc.identifier.urihttp://hdl.handle.net/10722/129382-
dc.description.abstractVitamin D(3) upregulated protein 1 (VDUP1) is a candidate tumor suppressor, the expression of which is dramatically reduced in various tumor tissues. In this study, we found that VDUP1 expression is suppressed during human hepatic carcinogenesis, and mice lacking VDUP1 are much more susceptible to diethylnitrosamine-induced hepatocarcinogenesis compared with wild type mice. VDUP1-deficient tumors proliferated significantly more than wild type tumors and had corresponding changes in the expression of key cell cycle regulatory proteins. In addition, the hepatomitogen-induced response was associated with a considerable increase in the release of TNF-alpha and subsequent enhancement of NF-kappaB activation in VDUP1-deficient mice. When cells were treated with TNF-alpha, the VDUP1 level was markedly reduced, concomitant with elevated NF-kappaB activation. Furthermore, the overexpression of VDUP1 resulted in the robust suppression of TNF-alpha-activated NF-kappaB activity via association with HDAC1 and HDAC3. These results indicate that VDUP1 negatively regulates hepatocarcinogenesis by suppressing TNF-alpha-induced NF-kappaB activation.-
dc.languageengen_US
dc.publisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.orgen_US
dc.relation.ispartofJournal of Immunology-
dc.subject.meshCarcinoma, Hepatocellular - metabolism-
dc.subject.meshCarrier Proteins - metabolism-
dc.subject.meshLiver Neoplasms - metabolism-
dc.subject.meshNF-kappa B - metabolism-
dc.subject.meshThioredoxins - metabolism-
dc.titleVitamin D3 upregulated protein 1 suppresses TNF-α–induced NF-κB activation in hepatocarcinogenesisen_US
dc.typeArticleen_US
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-1767&volume=185&issue=7&spage=3980&epage=3989&date=2010&atitle=Vitamin+D3+Upregulated+Protein+1+Suppresses+TNF-α–Induced+NF-κB+Activation+in+Hepatocarcinogenesisen_US
dc.identifier.emailShao, Y: yshao@HKUCC-COM.hku.hken_US
dc.identifier.emailKim, HC: hckim@kribb.re.kr-
dc.identifier.emailChoi, I: ipchoi@kribb.re.kr-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.4049/jimmunol.1000990-
dc.identifier.pmid20826751-
dc.identifier.scopuseid_2-s2.0-77958133863-
dc.identifier.hkuros183601en_US
dc.identifier.volume185en_US
dc.identifier.issue7-
dc.identifier.spage3980en_US
dc.identifier.epage3989-
dc.identifier.isiWOS:000282059500024-

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