Transfection of α(1,3)fucosyltransferase antisense sequences impairs the proliferative and tumorigenic ability of human colon carcinoma cells
✍ Scribed by Kara M. Hiller; John P. Mayben; Katharine M. Bendt; George A. Manousos; Kate Senger; H. Scott Cameron; Brent W. Weston
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 185 KB
- Volume
- 27
- Category
- Article
- ISSN
- 0899-1987
No coin nor oath required. For personal study only.
✦ Synopsis
Sialyl Lewis x and sialyl Lewis a are oncodevelopmental antigens involved in the pathogenesis of colon adenocarcinoma. Biosynthesis of these glycans is controlled by a(1,3/1,4)fucosyltransferases. We report the disruption of sialyl Lewis x/a biosynthesis and inhibition of colon carcinoma cell proliferation by stable transfection of antisense sequences directed at the human Lewis a(1,3/1,4)fucosyltransferase gene, FUT3, and the plasma a(1,3)fucosyltransferase gene, FUT6. COLO-205 cells expressed high levels of sialyl Lewis x/a, a(1,3)fucosyltransferase activity, and FUT3/6 transcripts, but COLO-205±derived antisense transfectant cell lines AS5C and AS7A did not. Sense transfectant S6G expressed higher levels of fucosyltransferase than parental COLO-205. Cellular proliferation assays showed marked correlative decreases in the growth of antisense lines and, conversely, increased growth of sense transfectants. Subcutaneous tumors created by injection of nude mice with antisense transfectant cell lines grew more slowly than those arising from control COLO-205 and sense transfectants. These results provide target validation for inhibition of carcinoma proliferation with antisense sequences directed at human fucosyltransferases. Mol.