Overexpression of fucosyltransferase IV in A431 cell line increases cell proliferation

Department of Pediatrics, Northwestern University, Evanston, Illinois, United States
The International Journal of Biochemistry & Cell Biology (Impact Factor: 4.05). 02/2007; 39(9):1722-30. DOI: 10.1016/j.biocel.2007.04.024
Source: PubMed


Fucosyltransferase IV is an essential enzyme that catalyzes the synthesis of fucosylated oligosaccharides by transferring GDP-fucose to the terminal N-acetylglucosamine with the alpha1,3-linkage. Lewis Y oligosaccharide has a terminal alpha1,3-linked fucose residue and elevation of Lewis Y level is seen in many epithelial cancers. The mechanism of Lewis Y elevation in neoplastic cells is still largely unknown. To study the impact of fucosyltransferase IV on Lewis Y expression and its role on neoplastic cell proliferation, a pEGFP-N1-FUT4 recombinant plasmid was developed and stably transfected into A431 cells. We found that fucosyltransferase IV overexpression promoted cell proliferation and increased the expression of proliferating cell nuclear antigen that correlated with Lewis Y augmentation. Cell cycle analysis demonstrated that fucosyltransferase IV overexpression facilitated cell cycle progression. In conclusion, fucosyltransferase IV overexpression augments Lewis Y expression to trigger neoplastic cell proliferation. These studies suggest that fucosyltransferase IV may serve as a potential therapeutic target for the treatment of Lewis Y-positive epithelial cancers.

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    • "LeY is carried by the glycoproteins and glycolipids on cell surface, catalyzed by FUT1 or FUT4. LeY is highly expressed in 60-90% of human epithelial-origin cancer , including breast, colon, lung, and gastric cancers [5] [6]. COX-2 is highly expressed at the early stage of cancers, being responsible for most of the prostanoid production *Address correspondence to this author at the "
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    ABSTRACT: Monoclonal antibody-based treatments of cancer which serve as magic 'bullets' have been established as one of the most successful therapeutic strategies. A variety of antigens has been investigated as targets for the mAb therapy of gastric cancer, including the carbohydrate type 2 blood group antigen. LewisY (LeY) is overexpressed on tumor cells surface either as glycolipids or glycoproteins. LeY is difucosylated oligosaccharide with the chemical structure [Fucα1→2Galβ1→ 4(Fucα1→3) GlcNAcβ1→R], which is catalyzed by fucosyltransferases, such as FUT 1 (α1→2) and FUT 4 (α1→3). The role of LeY antigen in cancer treatment and prevention has been extensively studied. Moreover, the cyclooxygenase-2 (COX-2) is an early event protein, highly expressed in H. pylori-related gastric cancer. COX-2 may play a pivotal part in the maintenance of tumor viability, growth, and metastasis. The COX-2 is upregulated in a variety of cancers, including gastric cancer. However, its inhibition may prevent or reverse gastric carcinogenesis. H. pylori mediated alteration of COX-2 through MAPKs pathway is one of the mechanisms that is implicated in gastric cancer. We have found COX-2 and LeY to be correlative sources of specific gastric biomarkers in gastric cancer, which is upregulated in the gastric cancer through MAPKs pathway. In addition, the anti-LeY antibody significantly downregulated the COX-2 expression through MAPKs pathway, helpful to the treatment of gastric cancer. In this review, we summarize the therapeutic effect of anti-LeY antibody, including the crucial role of COX-2 and LeY antigen in gastric cancer and discuss the COX-2 inhibition by anti-LeY antibody through MAPKs pathway.
    Current drug targets 02/2014; · 3.02 Impact Factor
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    • "Cell molecules are glycosylated by a series of glycosyltransferases resulting in glycan structures changes that may vary according to the physiological status of the organ [21]. FUTs are one type of these enzymes involved in glycosylation and their expressions have been studied in gastrointestinal carcinoma cell lines, gastric cancer cell lines, colon cancer cell lines, colorectal carcinoma tumor; prostate cancer cell lines, and ovarian carcinoma tumors cell lines [3, 4, 7, 10, 14, 23, 29, 30]. Nearly, most of all malignant cells demonstrate alterations in their glycosylation patterns when compared to their normal counter-part. "
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    ABSTRACT: Prostatic Adenocarcinoma (PA) and Benign Prostatic Hyperplasia (BPH) have their etiology not fully understood mainly in glycidic aspects. Glycan changes are associated with cell alterations where glycosylation is carried out by glycosyltransferases, such as fucosyltransferases (FUTs). These enzymes catalyze the insertion of L-fucose residues in a variety of glycan structures often in the final stage of glycosylation. The present study aimed to investigate the expression of FUT3 and FUT6 in PA and BPH as well as to correlate immunostaining of these transferases with PA clinic-histopathologic data. The FUT3 and FUT6 expressions were evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded biopsies of PA (n=40) and BPH (n=40). FUT3 and FUT6 showed a high expression in both prostatic diseases, especially FUT6. FUT6 was more immunoexpressed in PA cases than the FUT3 (p<0.0001) as well as in BPH cases but in a not significant way (p=0.0661). Besides, FUT3 was more expressed in BHP lesion than in PA cases (p<0.0001). Our study presented a new data about FUT3 and FUT6 expression in PA and BPH, revealing high FUT6 expression in both lesions and FUT3 overexpression in BHP in relation to PA, proposing that this enzyme could be a promising biomarker for benign prostate alterations.
    Acta histochemica et cytochemica official journal of the Japan Society of Histochemistry and Cytochemistry 06/2013; 46(3):105-9. DOI:10.1267/ahc.13010 · 1.39 Impact Factor
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    • "FUT4 interfered plasmid (FUT4-siRNA) and FUT4 overexpression plasmid (FUT4-cDNA) were constructed as before (Yang et al., 2007; Zhang et al., 2008). Cells were seeded on to 6-well plates. "
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    ABSTRACT: Adhesion molecules expressed on the uterine endometrium are potential receptive markers in embryo implantation. RL95-2 and HEC-1A cell lines represent the high- and low-receptive endometrial epithelium respectively. LeY (Lewis Y) is a difucosylated oligosaccharide highly expressed in the endometrium of some species during implantation. α1, 3 fucosylation of LeY is catalysed by FUT4 (fucosyltransferase IV), the key synthesis enzyme for LeY. We investigated whether the difference in receptivity between the 2 cell lines was related to different expressions of LeY and FUT4. RL95-2 cells expressed a higher level of LeY and FUT4 than HEC-1A cells, as shown by immunofluorescent staining, RT-PCR (reverse transcription-PCR) or Western blotting. FUT4-siRNA (small interfering RNA) transfection down-regulated FUT4 and LeY in RL95-2 cells, and inhibited the adhesion of the embryonic cells (JAR) to RL95-2 cell monolayer. FUT4-cDNA, however, increased the expression of FUT4 and LeY in HEC-1A cells, and increased the adhesion of embryonic cells to HEC-1A cell monolayer. Alterations of LeY level by up- or down-regulation of FUT4 also mediated EGFR (epidermal growth factor receptor)/MAPK (mitogen-activated protein kinase) signalling pathway. To conclude, the expression of LeY and FUT4 correlates with endometrial receptivity, making them potential new markers for the evaluation of endometrial receptivity.
    Cell Biology International 12/2011; 36(5):469-74. DOI:10.1042/CBI20100644 · 1.93 Impact Factor
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