Aberrant upregulation of ASCL2 by promoter demethylation promotes the growth and resistance to 5-fluorouracil of gastric cancer cells

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dc.contributor.authorOh Hyung Kwon-
dc.contributor.authorJong Lyul Park-
dc.contributor.authorSu Jin Baek-
dc.contributor.authorS M Noh-
dc.contributor.authorK S Song-
dc.contributor.authorSeon-Young Kim-
dc.contributor.authorYong Sung Kim-
dc.date.accessioned2017-04-19T09:37:23Z-
dc.date.available2017-04-19T09:37:23Z-
dc.date.issued2013-
dc.identifier.issn1347-9032-
dc.identifier.uri10.1111/cas.12076ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/11244-
dc.description.abstractAchaete scute-like 2 (ASCL2), a basic helix-loop-helix transcription factor, plays an essential role in the maintenance of adult intestinal stem cells. However, the function of ASCL2 in gastric cancer (GC) is poorly understood. Therefore, we investigated the roles and regulatory transcription mechanisms of ASCL2 in GC. Gene expression and methylation data analysis showed that ASCL2 was upregulated and hypomethylated in GC tissues. Using real-time RT-PCR and pyrosequencing analysis, we confirmed that ASCL2 was overexpressed and hypomethylated in GC tissues compared to adjacent normal tissues. We then investigated the mechanisms underlying the aberrant expression of ASCL2 in GC and found that treatment with a methylation inhibitor induced ASCL2 expression in GC cell lines. MBD-sequencing assay also revealed hypermethylation of the promoter region of ASCL2 in GC cell lines, which barely expressed the ASCL2 gene. Furthermore, ASCL2 expression levels were inversely correlated with GC patient survival. Ectopic overexpression of ASCL2 showed that ASCL2 increased cell growth and promoted resistance to 5-fluorouracil in GC cells. These results suggest that ASCL2 might play an important role in gastric tumor growth and chemoresistance, and could be a useful prognostic marker for GC patients.-
dc.publisherWiley-
dc.titleAberrant upregulation of ASCL2 by promoter demethylation promotes the growth and resistance to 5-fluorouracil of gastric cancer cells-
dc.title.alternativeAberrant upregulation of ASCL2 by promoter demethylation promotes the growth and resistance to 5-fluorouracil of gastric cancer cells-
dc.typeArticle-
dc.citation.titleCancer Science-
dc.citation.number3-
dc.citation.endPage397-
dc.citation.startPage391-
dc.citation.volume104-
dc.contributor.affiliatedAuthorOh Hyung Kwon-
dc.contributor.affiliatedAuthorJong Lyul Park-
dc.contributor.affiliatedAuthorSu Jin Baek-
dc.contributor.affiliatedAuthorSeon-Young Kim-
dc.contributor.affiliatedAuthorYong Sung Kim-
dc.contributor.alternativeName권오형-
dc.contributor.alternativeName박종열-
dc.contributor.alternativeName백수진-
dc.contributor.alternativeName노승무-
dc.contributor.alternativeName송규상-
dc.contributor.alternativeName김선영-
dc.contributor.alternativeName김용성-
dc.identifier.bibliographicCitationCancer Science, vol. 104, no. 3, pp. 391-397-
dc.identifier.doi10.1111/cas.12076-
dc.description.journalClassY-
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Aging Convergence Research Center > 1. Journal Articles
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