RRC ID 42539
Author Serpa J, Mesquita P, Mendes N, Oliveira C, Almeida R, Santos-Silva F, Reis CA, LePendu J, David L.
Title Expression of Lea in gastric cancer cell lines depends on FUT3 expression regulated by promoter methylation.
Journal Cancer Lett
Abstract Aberrant expression of Lewis antigens has been demonstrated in gastric lesions, namely gastritis, intestinal metaplasia (IM) and gastric carcinoma (GC), and can be partly due to overexpression of the Lewis (FUT3) enzyme. Our aim was to evaluate the role of promoter methylation in FUT3 and Le(a) expression in gastric carcinoma cell lines. MKN45 cell line showed low amounts of Le(a), in the absence of FUT3; GP220 expressed high levels of Le(a) and FUT3. After 5aza-2'deoxycytidine MKN45 showed increased levels of FUT3 and Le(a), by immunohistochemistry and Real-Time PCR, whereas GP220 showed an increase in FUT3 without increase of Le(a). Enzyme activity assays confirmed an increase in alpha-1,4 fucosyltransferase activity in both cell lines by 5aza-2'deoxycytidine. Luciferase reporter gene assays, using methylated and unmethylated deletion constructs of FUT3 promoter, showed that FUT3 expression is regulated by methylation. Summing up, we showed that FUT3 overexpression in gastric cells depends upon promoter hypomethylation and that FUT3 is responsible for overexpression of Le(a) in gastric cells, in vitro. FUT3, Lea, Methylation.
Volume 242(2)
Pages 191-7
Published 2006-10-28
DOI 10.1016/j.canlet.2005.11.009
PII S0304-3835(05)00988-2
PMID 16427187
MeSH Antigens, Neoplasm / biosynthesis* Azacitidine / analogs & derivatives Azacitidine / pharmacology Cell Line, Tumor DNA Methylation DNA Primers / chemistry Decitabine Fucosyltransferases / biosynthesis* Gene Expression Regulation, Neoplastic* Humans Immunohistochemistry Luciferases / metabolism Plasmids / metabolism Promoter Regions, Genetic* Reverse Transcriptase Polymerase Chain Reaction Stomach Neoplasms / metabolism*
IF 6.508
Times Cited 31
Human and Animal Cells