Glycobiology Advance Access originally published online on July 31, 2006
Glycobiology 2006 16(10):916-925; doi:10.1093/glycob/cwl022
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Genetic mechanisms for the synthesis of fucosyl GM1 in small cell lung cancer cell lines
2 Department of Biochemistry II, Nagoya University School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan; 3 Department of Internal Medicine II, Nagoya City University School of Medicine, 1 Kawasumi, Mizuho-ku, Nagoya 467-8602, Japan; and 4 Department of Neurology, Kinki University School of Medicine, 377-2 Ohno-higashi, Sayama, Osaka 589-8511, Japan
1 To whom correspondence should be addressed; e-mail: koichi{at}med.nagoya-u.ac.jp
Received on November 26, 2005; revised on July 9, 2006; accepted on July 10, 2006
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 
1,2-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 1,2-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.
Key words: fucosyl GM1 / fucosyltransferase / H enzyme / small cell lung cancer