ALTERED MESSENGER-RNA EXPRESSION OF SPECIFIC MOLECULAR-SPECIES OF FUCOSYL-TRANSFERASES AND SIALYL-TRANSFERASES IN HUMAN COLORECTAL-CANCER TISSUES

Human colorectal cancers express various cancer-associated carbohydrat e determinants such as Lewis Y or sialyl Lewis A, suggesting a conside rable alteration in glycosyltransferase activities occurring upon mali gnant transformation. We investigated the mRNA amounts of fucosyltrans ferase (Fuc-T) and sialyltransferase (ST) isoenzymes, including Fuc-T III, (V, V, VI and VII and ST-3N, ST-3O and ST-4, in human colorectal cancer tissues by Northern blotting and RT-PCR. Regarding fucosyltrans ferases, mRNA of Fuc-T III and VI was not significantly altered, and o nly fuc-T IV mRNA showed a moderate increase in cancer tissues when co mpared with adjacent non-malignant colonic epithelia taken from the sa me patient(273 +/- 96%; p < 0.001). The moderate increase of Fuc-T IV message may be related to an enhanced expression of Lewis Y in colon c ancer tissues. In the ST isoenzymes, mRNA for ST-3N remained unchanged , whereas that for ST-4 decreased significantly in cancer tissues, to 32 +/- 29%, (p < 0.005). The most remarkable finding was that the mess age of ST-3O was prominently increased in cancer tissues compared with non-malignant colorectal mucosa. When further investigated by quantit ative RT-PCR assays on a larger series of patients with colorectal can cers, the average increase in mRNA for ST-3O was 459 +/- 200% compared with that in adjacent non-malignant epithelium (significant at p < 0. 0001), The increase of ST-3O message was more prominent in the cancer tissues strongly expressing sialyl Lewis A than in the cancer tissues expressing sialyl Lewis A only weakly or moderately (significant at p < 0.05). The marked increase in the message of ST-3O is suggested to b e related to an enhanced expression of sialylated carbohydrate determi nants in colon cancer tissues including sialyl Lewis A, since the enzy me exhibited a significant activity against the type I chain carbohydr ate substrate and produced the precursors for sialyl Lewis A synthesis , when its cDNA was expressed in Cos-7 cells. (C) 1997 Wiley-Liss, Inc .