Structure and Expression of H-type GDP-L-Fucose:β-D-Galactoside 2-α-L-Fucosyltransferase Gene (FUT1): TWO TRANSCRIPTION START SITES AND ALTERNATIVE SPLICING GENERATE SEVERAL FORMS OF FUT1 mRNA

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The expression of the ABO antigens on erythrocyte membranes is regulated by H gene (FUT1)-encoded alpha(1,2)fucosyltransferase activity. We have examined the expression of the FUT1 in several tumor cell lines, including erythroid lineage and normal bone marrow cells, by Northern blot and/or reverse transcription-polymerase chain reaction (RT-PCR) analyses. RT-PCR indicated that bone marrow cells, erythroleukemic cells (HEL), and highly undifferentiated leukemic cells (K562) that have erythroid characteristics expressed the FUT1 mRNA while four leukemic cell lines did not. The FUT1 mRNA was also demonstrated in gastric, colonic, and ovarian (MCAS) cancer cell lines by RT-PCR. Northern blot analysis indicated that a 4. 0-kilobase FUT1 transcript was expressed in some of these tumor cell lines. Rapid amplification of 5' cDNA end (RACE) analysis suggested that the FUT1 transcript had several forms generated by two distinct transcription start sites and alternative splicing. The results of RT-PCR using specific primers for each starting exon suggested that two transcription initiation sites (exon 1A and exon 2A) of the FUT1 were identified in gastric cancer cells and in ovarian cancer cells. Only exon 1A was identified as a transcription start site in another gastric cancer cell line, two colonic cancer cell lines, and in K562 cells, whereas only exon 2A was identified in HEL cells and in bone marrow cells. These two transcription start sites were located 1.8 kilobases apart. Therefore, two distinct promoters appeared to be present in the FUT1. The distinct promoters of the FUT1 and alternative splicing of the FUT1 mRNA may be associated with time- and tissue-specific expression of the FUT1.