Methylation status of T-lymphoma invasion and metastasis 1 promoter and its overexpression in colorectal cancer
Methylation status of T-lymphoma invasion and metastasis 1 promoter and its overexpression in colorectal cancer
复制标题
T淋巴瘤侵袭转移1启动子甲基化状态及其在结直肠癌中的过表达
DOI：
10.1016/j.humpath.2010.08.013
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发表时间：
2011-04-01
期刊：
影响因子：
3.3
通讯作者：
Ding, Yanqing
中科院分区：
文献类型：
--
作者：
Jin, He;Li, Tingting;Ding, Yanqing
T淋巴瘤侵袭和转移I与肿瘤侵袭和转移有关。然而，人类结直肠癌中异常 T 淋巴瘤侵袭和转移表达的调节机制尚未明确。为了探讨甲基化状态与T淋巴瘤侵袭和转移I基因表达水平之间的关系，对232例匹配的人结直肠癌组织和正常结直肠粘膜样本进行甲基化特异性聚合酶链反应和免疫组织化学染色。结果显示，T 淋巴瘤侵袭和转移 1 蛋白在结直肠癌中过度表达，尤其是在转移病例中 (P < .001)。癌组织中T淋巴瘤侵袭转移1启动子甲基化程度略低于匹配正常粘膜(P < .05)，且T淋巴瘤侵袭转移I的表达水平与癌组织中甲基化状态呈负相关(P < .001)。用去甲基化剂 5-aza-2'-deoxycytidine 处理结肠癌细胞系 HT29 和 LS174T，导致启动子低甲基化，并伴随 T 淋巴瘤侵袭和转移 1 mRNA 和蛋白的重新表达。相比之下，结肠癌细胞系SW620和LoVo用高甲基化剂S-腺苷甲硫氨酸处理，导致T淋巴瘤侵袭和转移1启动子高甲基化，同时抑制T-淋巴瘤侵袭和转移I表达并抑制细胞生长，平板集落。形成和迁移。本研究表明结直肠癌组织中T淋巴瘤侵袭转移1的过表达与T淋巴瘤侵袭转移1启动子区的低甲基化状态相关。这表明T淋巴瘤侵袭和转移1的启动子低甲基化可能在结直肠癌的进展和转移中发挥作用。药理学逆转 T 淋巴瘤侵袭和转移 1 启动子低甲基化可能会抑制细胞增殖和迁移。 (C) 2011 Elsevier Inc. 保留所有权利。
T-lymphoma invasion and metastasis I has been implicated in tumor invasion and metastasis. However, the regulatory mechanisms underlying aberrant T-lymphoma invasion and metastasis expression in human colorectal cancer have not been well defined. To investigate the relationship between methylation status and expression levels of T-lymphoma invasion and metastasis I gene, methylation-specific polymerase chain reaction, and immunohistochemistry staining were performed in 232 matched samples of human colorectal cancer tissue and normal colorectal mucosa. Results showed that T-lymphoma invasion and metastasis 1 protein was overexpressed in colorectal cancer, especially in metastatic cases (P < .001). The degree of T-lymphoma invasion and metastasis 1 promoter methylation was a little lower in cancer tissues than in matched normal mucosa (P < .05), and the expression level of T-lymphoma invasion and metastasis I was inversely related to the methylation status in cancer tissues (P < .001). Colon cancer cell lines HT29 and LS174T were treated with demethylating agent 5-aza-2'-deoxycytidine, resulting in promoter hypomethylation accompanied by reexpression of T-lymphoma invasion and metastasis 1 mRNA and protein. In contrast, colon cancer cell lines SW620 and LoVo were treated with hypermethylation agent S-adenosylmethionine, resulting in T-lymphoma invasion and metastasis 1 promoter hypermethylation, accompanied by suppression of T-lymphoma invasion and metastasis I expression and inhibition of cell growth, plate colony. formation, and migration. The present study demonstrates that overexpression of T-lymphoma invasion and metastasis 1 is associated with hypomethylation status of T-lymphoma invasion and metastasis 1 promoter region in colorectal cancer tissues. It suggests that promotor hypomethylation of T-lymphoma invasion and metastasis 1 may play a role in the progression and metastasis of colorectal cancer. Pharmacologic reversal of T-lymphoma invasion and metastasis 1 promoter hypomethylation may inhibit cell proliferation and migration. (C) 2011 Elsevier Inc. All rights reserved.