[
Abstract]
[
Full Text PDF] (in Japanese / 5199KB)
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J.Jpn. Surg. Soc.. 97(2): 115-122, 1996
Feature topic
MOLECULAR BIOLOGY OF LEWIS ANTIGENS-HISTO-BLOOD TYPE ANTIGENS AND SIALYL LEWIS ANTIGENS AS TUMOR ASSOCIATED ANTIGENS-
The biosynthetic pathways of the Lewis histo-blood type antigens, Lewis a (Le
a) and Lewis b (Le
b), in correlation with ABH antigen synthesis and the synthesis of sialyl Lewis antigens, sialyl Lewis a (sLe
a) and sialy Lewis x (sLe
x), known as tumor associated antigens are described based on the recent molecular biological studies.
Individuals are divided by their erythrocyte Lewis antigen phenotypes into three types, Le (a+b-) which has Le
a antigen but not Le
b antigen, Le (a- b+) which has Le
b but not Le
a, and Le (a-b-) having neither Le
a nor Le
b. It was verified that Le (a-b-) individuals are the homozygotes with the nonfunctional
Lewis gene (
Le gene) which is inactivated by the missense mutations. Two kinds of the inactivated Le gene alleles were found in the Japanese population, and named
le1 and
le2. Individuals having a Le (a+b-) or a Le (a-b-) -non-secretor phenotype are the mutants who lack the secretor enzyme (Se enzyme) activity. The
Se gene encoding the Se enzyme has been recently cloned and analyzed for the mutation resulting in inactivation of the Se enzyme of the non-secretor individuals. Our
Se gene mutant analyses on the Japanese population ensured that the
Se gene is responsible for synthesis of the Le
b antigen. Mutant analyses of the other genes,
H gene and
FucTVI gene, which are also involved in the synthesis of Lewis antigens are described.
We recently demonstrated that the sLe
a antigen is the product of the
Lewis gene since all
le/le patients, who are determined as the genuine Lewis negative individuals by
Le genotyping, did not express any kinds of type l chain Lewis antigens (Le
a, Le
b and sLe
a) in their digestive organs. It is, therefore, unuseful to measure the CA19-9 titer of the genuine Lewis negative cancer patients.
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