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Glycobiology Advance Access published online on July 31, 2006

Glycobiology, doi:10.1093/glycob/cwl022
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Received November 26, 2005
Revised July 9, 2006
Accepted July 10, 2006

Article

Genetic mechanisms for the synthesis of fucosyl GM1 in small cell lung cancer cell lines

Noriyo Tokuda 1, Qing Zhang 1, Shoko Yoshida 2, Susumu Kusunoki 3, Takeshi Urano 1, Keiko Furukawa 1, and Koichi Furukawa 1 *

1 Department of Biochemistry II, Nagoya University School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065
2 Department of Biochemistry II, Nagoya University School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065; Department of Internal Medicine II, Nagoya City University School of Medicine, 1 Kawasumi, Mizuho-ku, Nagoya 467-8602
3 Department of Neurology, Kinki University School of Medicine, 377-2 Ohno-higashi, Sayama, Osaka 589-8511 Japan

* To whom correspondence should be addressed.
Koichi Furukawa, E-mail: koichi{at}med.nagoya-u.ac.jp


   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 lines expressing fucosyl GM1, both FUT1 and FUT2 mRNAs were detected, indicating that either one or both of {alpha}1,2-fucosyltransferases may be involved in the expression of fucosyl GM1. However, three out of these 4 lines contained function-loss mutations in the FUT2 coding region, suggesting that FUT1 is mainly involved in the {alpha}1,2-fucosylation of GM1. Expression levels of the GM1 synthase gene showed no correlation with those of fucosyl GM1, while 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, co-transfection of GD3 synthase cDNA reduced the expression levels of fucosyl GM1 with FUT1 or FUT2. Consequently, FUT1 seems to mainly contribute in 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.

Keywords: fucosyl GM1/small cell lung cancer/fucosyltransferase/H enzyme.
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