Increased expression of UDP-galactose transporter messenger RNA in human colon cancer tissues and its implication in synthesis of Thomsen-Friedenreich antigen and sialyl Lewis A/X determinants.

Abstract

A series of human nucleotide sugar transporters of the Golgi apparatus was recently cloned, including the transporters for UDP-galactose (UDP-Gal), UDP-N-acetylglucosamine (UDP-GlcNAc) and CMP-sialic acid (CMP-SA). We have examined the mRNA expression of these three transporters in human colon cancer tissues by reverse transcription-PCR analysis and compared it with that in nonmalignant colonic mucosa prepared from the same patients. The amount of mRNA for UDP-Gal transporter was significantly increased in colon cancer tissues compared with nonmalignant mucosa tissues (P = 0.035; n = 20). The increase was more prominent in patients with advanced colorectal cancer of Dukes' stages C and D, in which the amount of UDP-Gal transporter mRNA in cancer tissues showed on average about a 3.6-fold increase over the paired nonmalignant mucosa (statistically significant at P = 0.004; n = 14). The mRNA content of the other two transporters showed no significant difference between the paired cancer and normal tissues. When UDP-Gal transporter cDNA was stably transfected to cultured human colon cancer cells, the expression of Thomsen-Friedenreich (TF) antigen and of sialyl Lewis A (NeuAcalpha2-->3Galbeta1-->3[Fucalpha1-->4]GlcNAcbeta1-->R) and sialyl Lewis X (NeuAcalpha2-->3Galbeta1-->4[Fucalpha1-->3]GlcNAcbeta1-->R) determinants was significantly induced on transfectant cells, which resulted in markedly enhanced cell adhesion to vascular E-selectin. These findings suggest that the increase of UDP-Gal transporter mRNA is involved in the enhanced expression of cancer-associated carbohydrate determinants such as TF and sialyl Lewis A/X antigens in colon cancers.

• Authors: K Kumamoto, Y Goto, K Sekikawa, S Takenoshita, N Ishida, M Kawakita, R Kannagi
• Journal: Cancer research (Cancer Res) Vol. 61 Issue 11 Pg. 4620-7 (Jun 01 2001) ISSN: 0008-5472 [Print] United States
• PMID: 11389099 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Antigens, Tumor-Associated, Carbohydrate
• CA-19-9 Antigen
• Culture Media
• DNA, Complementary
• Gangliosides
• Monosaccharide Transport Proteins
• Oligosaccharides
• RNA, Messenger
• Sialyl Lewis X Antigen
• UDP-galactose translocator
• Thomsen-Friedenreich antigen
• sialyl Le(a) ganglioside
• Galactose

Topics

• Antigens, Neoplasm (biosynthesis)
• Antigens, Tumor-Associated, Carbohydrate (biosynthesis)
• CA-19-9 Antigen
• Colonic Neoplasms (genetics, immunology, metabolism)
• Culture Media
• DNA, Complementary (genetics)
• Galactose (metabolism)
• Gangliosides (biosynthesis)
• Gene Expression
• Humans
• Middle Aged
• Monosaccharide Transport Proteins (biosynthesis, genetics)
• Oligosaccharides (biosynthesis)
• RNA, Messenger (biosynthesis, genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Sialyl Lewis X Antigen
• Transfection
• Tumor Cells, Cultured