Elucidation for biological significance of cancer-associated carbohydrate antigens through genetic modification of carbohydrates

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Drastic alteration of carbohydrate antigens in carcinogenesis and metastasis were well-known phenomenon, and applied clinically as tumor markers. However, its molecular mechanism were hardly understood.In this project, we successfully cloned cDNAs for two novel glycosyltransferases, ST6GalNAc-I and β3Gal-T5, which were able to synthesize well-known cancer-associated antigens, sialyl Tn and CA19-9 respectively. The expression pattern of these enzymes were well correlated to that of respective antigens, strongly suggesting that these enzymes were physiological synthase of these cancer-associated antigens in the normal and cancer tissue.Thus, we transfected cDNAs of these enzymes into cells which did not express these antigens, and established several stable transformants, strongly expressing the antigens. Now we are investigating these cells for alteration of bilogical features both in vitro and in vivo models.