Over-expression of ST3Gal-I promotes mammary tumorigenesis

Gianfranco Picco, Sylvain Julien, Inka Brockhausen, Richard Beatson, Aristotelis Antonopoulos, Stuart Haslam, Ulla Mandel, Anne Dell, Sarah Pinder, Joyce Taylor-Papadimitriou, Joy Burchell

Research output: Contribution to journalArticlepeer-review

111 Citations (Scopus)

Abstract

Changes in glycosylation are common in malignancy, and as almost all surface proteins are glycosylated, this can dramatically affect the behavior of tumor cells. In breast carcinomas, the O-linked glycans are frequently truncated, often as a result of premature sialylation. The sialyltransferase ST3Gal-I adds sialic acid to the galactose residue of core 1 (Gal beta 1,3GalNAc) O-glycans and this enzyme is over-expressed in breast cancer resulting in the expression of sialylated core 1 glycans. In order to study the role of ST3Gal-I in mammary tumor development, we developed transgenic mice that over-express the sialyltransferase under the control of the human membrane-bound mucin 1 promoter. These mice were then crossed with PyMT mice that spontaneously develop mammary tumors. As expected, ST3Gal-I transgenic mice showed increased activity and expression of the enzyme in the pregnant and lactating mammary glands, the stomach, lungs and intestine. Although no obvious defects were observed in the fully developed mammary gland, when these mice were crossed with PyMT mice, a highly significant decrease in tumor latency was observed compared to the PyMT mice on an identical background. These results indicate that ST3Gal-I is acting as a tumor promoter in this model of breast cancer. This, we believe, is the first demonstration that over-expression of a glycosyltransferase involved in mucin-type O-linked glycosylation can promote tumorigenesis.
Original languageEnglish
Pages (from-to)1241 - 1250
Number of pages10
JournalGlycobiology
Volume20
Issue number10
DOIs
Publication statusPublished - Oct 2010

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