| Research Abstract |
Recently, it has been demonstrated that the carbohydrate chains expressed on cancer cell membranes contribute to tumor metastasis. It has also been reported that changes in the activity of glycosyltransferases involved in the synthesis of carbohydrate chains inhibit experimental metastasis. Accordingly, to determine how type 1 and 2 carbohydrate chains expressed by endometrial cancer are involved in tumor progression and metastasis, we analyzed the mechanism of expression of these carbohydrate chains at the level of galactose transferase, as well as alterations of the carbohydrate chains and tumor cell infiltration after transfer of the gene encoding the galactose transferase synthesizing type 2 carbohydrate chains. We devised a new assay to determine the activities of beta1,3-and beta1,4-galactose transferase (GT), which regulate the synthesis of type 1 and 2 carbohydrate chains. In cancer of the endometrium, beta1,3-GT activity was found to be lower than beta1,4-GT activity. Next, hu
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man beta1,4-GT cDNA was transferred into a cell line derived from endometrial cancer with low expression of beta1,4-GT,yielding a high beta1,4-GT expressing cell line with increased levels of beta1,4-GT mRNA and protein. The expression of a type 1 carbohydrate chain (nLc3Cer) was decreased in the high beta1,4-GT expressing cell line, while the expression of a type 2 carbohydrate chain (Lewis X) was increased. Expression of an adhesion molecule (integrin beta1) was similar in the vector control and high beta1,4-GT expressing cell lines. The high beta1,4-GT expressing cell line showed a high level of cellilar infiltration in vitro. Adhesion of this cell line to extracellular matrix proteins was also increased. These findings suggest that endometrial cancer has lower beta1,6-GT activity than beta1,4-GT activity and that high expression of beta1,4-GT is associated with increased cellular infiltration and adhesion. Accordingly, beta1,4-GT may be involved in the molecular mechanism of infiltration and metastasis of cancer of the endometrium. Less
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