title: Genetic mechanisms for the synthesis of fucosyl GM1 in small cell lung cancer cell lines.
abstract: Fucosyl GM1 has been reported to be specifically expressed in small cell lung cancer (SCLC) cells. However, the genetic basis for the synthesis of fucosyl GM1 has not been investigated. We analyzed the glycosyltransferases responsible for the synthesis of fucosyl GM1 in SCLC cell lines. In four SCLC cell lines expressing fucosyl GM1, both FUT1 and FUT2 mRNAs were detected, indicating that either one or both of alpha1,2-fucosyltransferases may be involved in the expression of fucosyl GM1. However, three of these four lines contained function-loss mutations in the FUT2 coding region, suggesting that FUT1 is mainly involved in the alpha1,2-fucosylation of GM1. The expression levels of the GM1 synthase gene showed no correlation with those of fucosyl GM1, whereas the co-transfection of GM1 synthase cDNA with FUT1 or FUT2 into SK-LC-17 clearly enhanced the neo-expression of fucosyl GM1, indicating its essential role. In contrast, the co-transfection of GD3 synthase cDNA reduced the expression levels of fucosyl GM1 with FUT1 or FUT2. Consequently, FUT1 seems to mainly contribute to the expression of fucosyl GM1, although both FUT1 and FUT2 are capable of generating the antigen. These results should promote the functional analysis of fucosyl GM1 leading to the development of novel therapies for SCLC.
authors.affiliation: Department of Biochemistry II, Nagoya University School of Medicine, Nagoya, Japan.
authors.forename: Noriyo
authors.initials: N
authors.lastname: Tokuda
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Shoko
authors.initials: S
authors.lastname: Yoshida
authors.forename: Susumu
authors.initials: S
authors.lastname: Kusunoki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Urano
authors.forename: Keiko
authors.initials: K
authors.lastname: Furukawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Furukawa
mesh_terms: D001789:Blood Group Antigens / Q000737:chemistry / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000378:metabolism*; D005643:Fucose / Q000378:metabolism; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism; D005677:G(M1) Ganglioside / Q000031:analogs & derivatives* / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009154:Mutation; D014162:Transfection; D014407:Tumor Cells, Cultured; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D001789:Blood Group Antigens; D005643:Fucose; D005647:Fucosyltransferases; D005677:G(M1) Ganglioside; D000097631:Galactoside 2-alpha-L-fucosyltransferase; C039123:fucosyl GM1 ganglioside