Cloning, expression, and characterization of a novel UDP-galactose:beta-N-acetylglucosamine beta1,3-galactosyltransferase (beta3Gal-T5) responsible for synthesis of type 1 chain in colorectal and pancreatic epithelia and tumor cells derived therefrom.

Abstract

The sialyl Lewis a antigen is a well known tumor marker, CA19-9, which is frequently elevated in the serum in gastrointestinal and pancreatic cancers. UDP-galactose:N-acetylglucosamine beta1, 3-galactosyltransferase(s) (beta3Gal-Ts) are required for the synthesis of the sialyl Lewis a epitope. In the present study, a novel beta3Gal-T, named beta3Gal-T5, was isolated from a Colo205 cDNA library using a degenerate primer strategy based on the amino acid sequences of the four human beta3Gal-T genes cloned to date. Transfection experiments demonstrated that HCT-15 cells transfected with the beta3Gal-T5 gene expressed all the type 1 Lewis antigens. In gastrointestinal and pancreatic cancer cell lines, the amounts of beta3Gal-T5 transcripts were quite well correlated with the amounts of the sialyl Lewis a antigens. The beta1,3Gal-T activity toward agalacto-lacto-N-neotetraose was also well correlated with the amounts of beta3Gal-T5 transcripts in a series of cultured cancer cells, and in Namalwa and HCT-15 cells transfected with the beta3Gal-T5 gene. Thus, the beta3Gal-T5 gene is the most probable candidate responsible for the synthesis of the type 1 Lewis antigens in gastrointestinal and pancreatic epithelia and tumor cells derived therefrom. In addition, beta3Gal-T5 is a key enzyme that determines the amounts of the type 1 Lewis antigens including the sialyl Lewis a antigen.

• Authors: S Isshiki, A Togayachi, T Kudo, S Nishihara, M Watanabe, T Kubota, M Kitajima, N Shiraishi, K Sasaki, T Andoh, H Narimatsu
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 274 Issue 18 Pg. 12499-507 (Apr 30 1999) ISSN: 0021-9258 [Print] United States
• PMID: 10212226 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CA-19-9 Antigen
• DNA, Complementary
• Gangliosides
• RNA, Messenger
• sialyl Le(a) ganglioside
• Transferases (Other Substituted Phosphate Groups)
• UDPgalactose - UDP-N-acetylglucosamine galactosephosphotransferase

Topics

• Amino Acid Sequence
• Base Sequence
• CA-19-9 Antigen
• Cloning, Molecular
• Colorectal Neoplasms (enzymology, immunology, pathology)
• DNA, Complementary
• Gangliosides (immunology)
• Humans
• Molecular Sequence Data
• Pancreatic Neoplasms (enzymology, immunology, pathology)
• RNA, Messenger (genetics)
• Sequence Homology, Amino Acid
• Transferases (Other Substituted Phosphate Groups) (genetics, metabolism)
• Tumor Cells, Cultured