Expression of Le(a) in gastric cancer cell lines depends on FUT3 expression regulated by promoter methylation

• Type: Article in International Scientific Journal
• Date: 2006

Authors

Serpa, J (Author) Other; Mesquita, P (Author) Other; Mendes, N (Author) Other; Oliveira, C (Author) Other; Raquel Almeida (Author) FMUP; Santos-Silva F (Author) FMUP; Celso Reis (Author) FMUP; LePendu, J (Author) Other; David L (Author) FMUP

Journal

Title: Cancer Letters

Vol. 242

Pages: 191-197

ISSN: 0304-3835

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 32 Citations

Scopus - 35 Citations

Other information

Authenticus ID: P-004-GHB

DOI: 10.1016/j.canlet.2005.11.009

Abstract (EN): 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 Lea and FUT3. After 5aza-2'deoxycytidine MKN45 showed increased levels of FUT3 and Le(a), by immunohistochernistry 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 hypornethylation and that FUT3 is responsible for overexpression of Le(a) in gastric cells, in vitro. FUT3, Lea, Methylation

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7