Open AccessAberrant upregulation of ASCL 2 by promoter demethylation promotes the growth and resistance to 5‐fluorouracil of gastric cancer cells
Author(s) -
Kwon OhHyung,
Park JongLyul,
Baek SuJin,
Noh SeungMoo,
Song KyuSang,
Kim SeonYoung,
Kim Yong Sung
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12076
Subject(s) - ectopic expression , biology , downregulation and upregulation , dna methylation , cancer research , methylation , transcription factor , microbiology and biotechnology , carcinogenesis , cancer , gene expression , gene , genetics
Achaete scute‐like 2 ( ASCL 2 ), a basic helix‐loop‐helix transcription factor, plays an essential role in the maintenance of adult intestinal stem cells. However, the function of ASCL 2 in gastric cancer ( GC ) is poorly understood. Therefore, we investigated the roles and regulatory transcription mechanisms of ASCL 2 in GC . Gene expression and methylation data analysis showed that ASCL 2 was upregulated and hypomethylated in GC tissues. Using real‐time RT ‐ PCR and pyrosequencing analysis, we confirmed that ASCL 2 was overexpressed and hypomethylated in GC tissues compared to adjacent normal tissues. We then investigated the mechanisms underlying the aberrant expression of ASCL 2 in GC and found that treatment with a methylation inhibitor induced ASCL 2 expression in GC cell lines. MBD ‐sequencing assay also revealed hypermethylation of the promoter region of ASCL 2 in GC cell lines, which barely expressed the ASCL 2 gene. Furthermore, ASCL 2 expression levels were inversely correlated with GC patient survival. Ectopic overexpression of ASCL 2 showed that ASCL 2 increased cell growth and promoted resistance to 5‐fluorouracil in GC cells. These results suggest that ASCL 2 might play an important role in gastric tumor growth and chemoresistance, and could be a useful prognostic marker for GC patients.