Aberrant Cosmc genes result in Tn antigen expression in human colorectal carcinoma cell line HT-29.
Aberrant Cosmc genes result in Tn antigen expression in human colorectal carcinoma cell line HT-29.
复制标题
DOI：
--
复制
发表时间：
2015-03
影响因子：
1.4
通讯作者：
Xiaofeng Yu;Zhenzhen Du;Xuhong Sun;Chuanqin Shi;Huaixiang Zhang;T. Hu
中科院分区：
文献类型：
--
作者：
Xiaofeng Yu;Zhenzhen Du;Xuhong Sun;Chuanqin Shi;Huaixiang Zhang;T. Hu
Tn抗原是最常见的肿瘤相关糖类抗原之一，由Cosmc基因突变而产生。COSMC位于X24中，由单个基因编码，作为T-合成酶的特异性分子伴侣发挥作用。虽然在正常细胞中不能检测到Tn抗原，但Cosmc突变会使T-合酶失活，从而导致某些癌症中Tn抗原的表达。除了这种Cosmc突变诱导的表达外，TN抗原还在Jurkat T、LSC和LS174T等细胞系中表达。目前尚不清楚结肠癌细胞株HT-29中是否存在Cosmc突变。在这里，我们从一名女性结肠癌患者的HT-29细胞中分离出HT-29-TN+细胞。这些HT-29-TN+细胞表现出COSMC基因编码序列(CDS)的缺失，导致T-合成酶活性和TN抗原表达缺失。此外，在男性患者的HT-29-TN+以及HT-29-TN-和TN-肿瘤细胞中几乎没有检测到Cosmc CpG岛甲基化。而在正常女性细胞中，Cosmc的CpG岛甲基化频率约为50%。根据SNP位点的检测，在HT-29-TN+和HT-29-TN-细胞中只存在一个Cosmc活性等位基因。这些结果表明，HT-29-TN+细胞中TN抗原的表达和T-合成酶的失活可能与Cosmc活性等位基因中CDS的缺失有关，而HT-29细胞中Cosmc的非活性等位基因缺失对Cosmc功能没有影响。
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.