80 0

Full metadata record

DC FieldValueLanguage
dc.contributor.author계명찬-
dc.date.accessioned2018-04-02T07:38:56Z-
dc.date.available2018-04-02T07:38:56Z-
dc.date.issued2011-11-
dc.identifier.citationLaborotory Investion, Nov 2011, 91(11), P.1652-1667, 16p.en_US
dc.identifier.issn0023-6837-
dc.identifier.urihttp://www.nature.com/articles/labinvest2011117-
dc.identifier.urihttp://hdl.handle.net/20.500.11754/54932-
dc.description.abstractThe tight junction (TJ) protein claudin-4 is aberrantly upregulated in gastric cancer, but its clinical significance and the molecular mechanisms underlying claudin-4 overexpression in gastric cancer remain unclear. Here, we investigated its roles and epigenetic mechanisms regulating CLDN4 expression in gastric cancer. We show that increased membranous expression of claudin-4 in gastric carcinoma is associated with better patient prognosis, whereas cytoplasmic claudin-4 expression did not show a significant association with prognosis. Consistent with the correlation of increased membranous claudin-4 with favorable clinicopathological factors, claudin-4 overexpression inhibited the migration and invasion of gastric cancer cells; in contrast, it did not affect cell growth. Claudin-4 expression also increased the barrier function of TJs. Claudin-4 upregulation was strongly correlated with DNA hypomethylation in both gastric tissues and gastric cancer cells. Moreover, CLDN4 expression was repressed in normal gastric tissues in association with bivalent histone modifications, and loss of repressive histone methylations and gain of active histone modifications were associated with CLDN4 overexpression in gastric cancer cells. Interestingly, CLDN4 repression could be markedly derepressed by combined treatments that simultaneously target both histone modifications and DNA demethylation in CLDN4-hypermethylated cells, whereas concomitant changes in histone methylations and acetylations are required for CLDN4 induction in CLDN4-repressed cells with low DNA methylation. Taken together, this study reveals that membranous claudin-4 expression is associated with gastric cancer progression and that it is an independent positive prognosis marker in gastric carcinoma. Furthermore, our findings suggest that epigenetic derepression may be a possible mechanism underlying CLDN4 overexpression in gastric cancer and that claudin-4 may have potential as a promising target for the treatment of gastric cancer. Laboratory Investigation (2011) 91, 1652-1667; doi:10.10en_US
dc.description.sponsorshipWe thank Dr Victor E Marquez for DZNep and we are grateful to Si Eun Kim for her technical assistance. This study was supported by grants from the Korea Healthcare Technology R&D project of the Ministry of Health, Welfare & Family Affairs (A084366), the National Research Foundation of Korea (NRF) by the Korea government (MEST) (No. 20090083533) and the R&D program of MKE/KEIT (10035329, Development of Antibody drug for new target protein related with ovarian cancer).en_US
dc.language.isoenen_US
dc.publisherNature Publishing Groupen_US
dc.subjectclaudin-4en_US
dc.subjectDNA methylationen_US
dc.subjectepigenetic derepressionen_US
dc.subjectgastric carcinomaen_US
dc.subjecthistone modificationen_US
dc.titleClaudin-4 overexpression is associated with epigenetic derepression in gastric carcinomaen_US
dc.typeArticleen_US
dc.relation.no11-
dc.relation.volume91-
dc.identifier.doi10.1038/labinvest.2011.117-
dc.relation.page1652-1667-
dc.relation.journalLABORATORY INVESTIGATION-
dc.contributor.googleauthorErkin, Ozgur Cem-
dc.contributor.googleauthorGye, Myung Chan-
dc.contributor.googleauthorShin, Young Kee-
dc.contributor.googleauthorKim, Seok-Hyung-
dc.contributor.googleauthorChoi, Yoon-La-
dc.contributor.googleauthorPark, Cheol Keun-
dc.contributor.googleauthorLee, Jae Eun-
dc.contributor.googleauthorKoh, Sang Seok-
dc.contributor.googleauthor계명찬-
dc.contributor.googleauthor신영기-
dc.contributor.googleauthor김석형-
dc.contributor.googleauthor최윤라-
dc.contributor.googleauthor박재은-
dc.contributor.googleauthor고상석-
dc.relation.code2011206260-
dc.sector.campusS-
dc.sector.daehakCOLLEGE OF NATURAL SCIENCES[S]-
dc.sector.departmentDEPARTMENT OF LIFE SCIENCE-
dc.identifier.pidmcgye-
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE