Galectin-7 is epigenetically-regulated tumor suppressor in gastric cancer.
Galectin-7 is epigenetically-regulated tumor suppressor in gastric cancer.
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DOI：
10.18632/oncotarget.1219
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发表时间：
2013-09
期刊：
影响因子：
--
通讯作者：
Chun KH
中科院分区：
文献类型：
--
作者：
Kim SJ;Hwang JA;Ro JY;Lee YS;Chun KH
胃癌是癌症死亡的第二大原因，由于预后不良和治疗选择有限，仍然是一个重大的临床挑战。因此，胃肿瘤发生的基本机制值得研究。尽管半乳糖苷结合凝集素 galectin-7 在癌症中的调节已被研究，但其在肿瘤形成和进展中的作用仍然存在争议。在这项研究中，我们研究了半乳糖凝集素 7 的表达及其在胃癌中的作用。使用胃癌患者组织微阵列进行的免疫组织化学染色显示，与匹配的正常组织相比，恶性组织中半乳糖凝集素 7 的表达水平显着降低，并且恶性组织中半乳糖凝集素 7 表达的降低与晚期 TMN 分期疾病相关（p = 0.034）。重要的是，正常组织中半乳糖凝集素 7 的低表达与较差的存活率相关（p = 0.0561）。 AGS 胃腺癌细胞中半乳糖凝集素 7 的过度表达抑制了细胞增殖、迁移和侵袭，而 KATO III 胃癌细胞中半乳糖凝集素 7 的去除则逆转了这些特性。过表达半乳糖凝集素7的AGS细胞不能在异种移植小鼠中形成胃肿瘤。在测试的 9 种胃癌细胞系中，有 7 种观察到超过 70% 的高甲基化，5-氮杂胞苷治疗通过减少来自 5 个不同器官来源的 24 种癌细胞系的甲基化来降低半乳糖凝集素 7 的表达。我们分析了半乳糖凝集素 7 基因组区域中的 CpG 岛，并检测到外显子 2（预测的 p53 结合区域）+1566bp 处的高甲基化。在 20 名患者的胃癌组织中也检测到该区域的 DNA 高甲基化。综上所述，我们的数据表明，galectin-7 具有肿瘤抑制功能，并且该基因通过 DNA 甲基化进行表观遗传修饰，并在胃癌中显着下调。对半乳糖凝集素 7 调节的进一步研究可能会改善胃癌的诊断和治疗。
Gastric cancer is the second leading cause of cancer death and remains a major clinical challenge due to poor prognosis and limited treatment options. Therefore, the basic mechanisms underlying gastric tumorigenesis deserve investigation. Although regulation of the galactoside-binding lectin galectin-7 in cancer has been studied, its role in tumor formation and progression remains controversial. In this study, we investigated galectin-7 expression and its role in gastric cancer. Immunohistochemical staining using a tissue microarray of gastric cancer patients revealed significantly low expression levels of galectin-7 in malignant tissues compared with matched normal tissues, and decreased expression of galectin-7 in malignant tissues was associated with advanced TMN stage disease (p =0.034). Importantly, low expression of galectin-7 in normal tissues was associated with a poor survival rate (p =0.0561). Over-expression of galectin-7 in AGS gastric adenocarcinoma cells suppressed cell proliferation, migration, and invasion, whereas ablation of galectin-7 in KATO III gastric carcinoma cells reversed these properties. AGS cells that overexpressed galectin-7 could not form gastric tumors in xenografted mice. More than 70% hypermethylation was observed in 7 of 9 gastric cancer cell lines tested and 5-aza-cytidine treatment lowered galectin-7 expression by reducing methylation in 24 cancer cell lines from five different organ origins. We analyzed CpG islands in the galectin-7 genomic region and detected hypermethylation at +1566bp of exon 2, the predicted p53 binding region. DNA hypermethylation of this region was also detected in gastric cancer tissues from 20 patients. Taken together, our data indicate that galectin-7 has a tumor suppressive function, and that the gene is epigenetically modified by DNA methylation and significantly down-regulated in gastric cancer. Further study of galectin-7 regulation may lead to improved gastric cancer diagnosis and therapy.
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