Altered mRNA expression of specific molecular species of fucosyl- and sialyl-transferases in human colorectal cancer tissues.
Human colorectal cancers express various cancer-associated carbohydrate determinants such as Lewis Y or sialyl Lewis A, suggesting a considerable alteration in glycosyltransferase activities occurring upon malignant transformation. We investigated the mRNA amounts of fucosyltransferase (Fuc-T) and sialyltransferase (ST) isoenzymes, including Fuc-T III, IV, V, VI and VII and ST-3N, ST-30 and ST-4, in human colorectal cancer tissues by Northern blotting and RT-PCR. Regarding fucosyltransferases, mRNA of Fuc-T III and VI was not significantly altered, and only Fuc-T IV mRNA showed a moderate increase in cancer tissues when compared with adjacent non-malignant colonic epithelia taken from the same 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 cancer 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 message of ST-30 was prominently increased in cancer tissues compared with non-malignant colorectal mucosa. When further investigated by quantitative RT-PCR assays on a larger series of patients with colorectal cancers, the average increase in mRNA for ST-30 was 459 +/- 200% compared with that in adjacent non-malignant epithelium (significant at p < 0.0001). The increase of ST-30 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-30 is suggested to be related to an enhanced expression of sialylated carbohydrate determinants in colon cancer tissues including sialyl Lewis A, since the enzyme exhibited a significant activity against the type 1 chain carbohydrate substrate and produced the precursors for sialyl Lewis A synthesis, when its cDNA was expressed in Cos-7 cells.
Ito
H
H
Laboratory of Experimental Pathology, Research Institute, Aichi Cancer Center, Nagoya, Chikusaku, Japan.
Hiraiwa
N
N
Sawada-Kasugai
M
M
Akamatsu
S
S
Tachikawa
T
T
Kasai
Y
Y
Akiyama
S
S
Ito
K
K
Takagi
H
H
Kannagi
R
R
D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D018395:CA-19-9 Antigen; D019556:COS Cells; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics; D004790:Enzyme Induction; D005260:Female; D005647:Fucosyltransferases / Q000096:biosynthesis* / Q000235:genetics; D005732:Gangliosides / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D012799:Sialyltransferases / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection
D000951:Antigens, Neoplasm; D018395:CA-19-9 Antigen; D005732:Gangliosides; D007527:Isoenzymes; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C064564:sialyl Le(a) ganglioside; D005647:Fucosyltransferases; D012799:Sialyltransferases