Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ABH antigens are expressed by colonic epithelial cells throughout the colon during fetal life but only in proximal segments during adulthood. Malignant and premalignant colonic tumors frequently exhibit ABH reappearance (distal lesions) or ABH deletion (proximal lesions) and occasionally express incompatible A or B substances. Mechanisms governing these developmental and cancer-associated alterations are unknown. Therefore, experiments were performed to assess the activities of biosynthetic (glycosyltransferase) and degradative (glycosidase) enzymes in normal and cancerous tissues of the proximal and distal colon. In normal colonic mucosa, A, B, and H transferase activities were similar in proximal and distal segments. Analysis of enzyme substrate affinities and product characterization confirmed that the ABH transferases in colonic tissues were similar to the gene-specified transferases in human serum. Glycosidase enzyme activities were also comparable in proximal and distal normal colon. Cancers had lower A and B transferase but similar H transferase activities compared with paired normal mucosa. Thus, the absence of ABH antigen expression in normal distal colon is not caused by insufficient glycosyltransferase activity or excessive glycosidase activity.
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PMID:Blood group antigen synthesis and degradation in normal and cancerous colonic tissues. 211 34

The synthesis of blood group ABH antigens is under genetic control, where the primary gene products are glycosyltransferases. Several studies have demonstrated cancer-associated alterations in ABH antigen expression in human colon cancer tissues. However, the mechanism(s) responsible for these alterations has not been elucidated. Therefore, experiments were conducted using nine established colon cancer cell lines (four type O, three type A, and two type B) to examine ABH antigen expression by immunocytochemistry and correlate this with activities of ABH biosynthetic (glycosyltransferase) and degradative (glycosidase) enzymes. The products of the glycosyltransferase enzymes were characterized by high performance liquid chromatography and paper chromatography, and substrate affinities (apparent Km values) of the cancer cell-derived glycosyltransferases were analyzed. The present data demonstrate: (a) all cell lines except H-498 (blood type A) expressed the appropriate ABH glycosyltransferase as well as all three glycosidases; (b) product characterization and substrate dependence experiments suggested that the cancer cell-derived ABH glycosyltransferase enzymes had properties that were similar to those of the ABH enzymes in human serum; (c) H-498 cells exhibited A antigen deletion with accumulation of H precursor substance, most likely due to insufficient A transferase activity; (d) SW1417 cells (blood type B) demonstrated B antigen deletion without precursor accumulation, despite adequate levels of B transferase and low alpha-galactosidase activity; and (e) weak incompatible A antigen expression occurred in LoVo (type B) and SW1116 (type O) cells, and weak incompatible B antigen expression occurred in H-498 (type A) and SW1116 cells. However, since these cells lacked incompatible A or B transferase activity, these incompatible antigens are probably not the true A or B antigens. Thus, the colon cancer cell lines used in this study exhibit all of the ABH alterations previously described in colon cancer tissues and appear to be useful experimental models for studying the molecular events involved in cancer-associated ABH expression.
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PMID:ABH blood group antigen expression, synthesis, and degradation in human colonic adenocarcinoma cell lines. 254 45