title: Aberrant Cosmc genes result in Tn antigen expression in human colorectal carcinoma cell line HT-29.
abstract: The Tn antigen, which arises from mutation in the Cosmc gene is one of the most common tumor associated carbohydrate antigens. Cosmc resides in X24 encoded by a single gene and functions as a specific molecular chaperone for T-synthase. While the Tn antigen cannot be detected in normal cells, Cosmc mutations inactivate T-synthase and consequently result in Tn antigen expression within certain cancers. In addition to this Cosmc mutation-induced expression, the Tn antigen is also expressed in such cell lines as Jurkat T, LSC and LS174T. Whether the Cosmc mutation is present in the colon cancer cell line HT-29 is still unclear. Here, we isolate HT-29-Tn+ cells from HT-29 cells derived from a female colon cancer patient. These HT-29-Tn+ cells show a loss of the Cosmc gene coding sequence (CDS) leading to an absence of T-synthase activity and Tn antigen expression. Additionally, almost no methylation of Cosmc CpG islands was detected in HT-29-Tn+ as well as in HT-29-Tn- and Tn- tumor cells from male patients. In contrast, the methylation frequency of CpG island of Cosmc in normal female cells was ~50%. Only one active allele of Cosmc existed in HT-29-Tn+ and HT-29-Tn- cells as based upon detection of SNP sites. These results indicate that Tn antigens expression and T-synthase inactivity in HT-29-Tn+ cells can be related to the absence of CDS in Cosmc active alleles, while an inactive allele deletion of Cosmc in HT-29 cells has no influence on Cosmc function.
authors.affiliation: Department of Immunology, Binzhou Medical University Yantai 264003, P.R. China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Immunology, Binzhou Medical University Yantai 264003, P.R. China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Du
authors.affiliation: Department of Essentials of Basic Medicine, Binzhou Medical University Yantai, P.R. China.
authors.forename: Xuhong
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Immunology, Binzhou Medical University Yantai 264003, P.R. China.
authors.forename: Chuanqin
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Immunology, Binzhou Medical University Yantai 264003, P.R. China.
authors.forename: Huaixiang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Binzhou Medical University Yantai 264003, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Hu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000096:biosynthesis* / Q000235:genetics; D002469:Cell Separation; D015179:Colorectal Neoplasms / Q000235:genetics*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D019073:HT29 Cells; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics*; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; C505369:C1GALT1C1 protein, human; D018832:Molecular Chaperones; C040286:Tn antigen
keywords: Cosmc; CpG methylation; T-synthase; Tn antigen; colon cancer