Impact of MUC1 mucin downregulation in the phenotypic characteristics of MKN45 gastric carcinoma cell line.
Impact of MUC1 mucin downregulation in the phenotypic characteristics of MKN45 gastric carcinoma cell line.
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DOI：
10.1371/journal.pone.0026970
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Santos-Silva F
中科院分区：
文献类型：
--
作者：
Costa NR;Paulo P;Caffrey T;Hollingsworth MA;Santos-Silva F
胃癌是世界范围内癌症相关死亡的第二大原因。与这种疾病相关的高死亡率部分是由于对胃癌发生的知识有限以及缺乏可用的治疗和预防策略。MUC 1是一种高分子量跨膜粘蛋白，在大多数腺上皮细胞的顶端表面表达，是胃粘膜上方粘液层的主要成分。在大约95%的人类腺癌中发现MUC 1的过表达，其中MUC 1与致癌活性相关。MUC 1在胃癌进展中的作用仍有待阐明。我们通过RNA干扰下调胃癌细胞系中MUC 1的表达，并研究其对细胞增殖（MTT测定）、凋亡（TUNEL测定）、迁移（迁移测定）、侵袭（侵袭测定）和聚集（聚集测定）的影响。通过微阵列分析评估整体基因表达，以鉴定受MUC 1表达调控的改变。还在小鼠中进行了体内测定，以研究MKN 45胃癌细胞系中MUC 1下调和未下调的细胞的致瘤性。与对照组相比，MUC 1表达下调增加了增殖和凋亡，而细胞-细胞聚集减少。在迁移和侵袭方面，下调的克隆和对照之间没有发现显著差异。TCN 1、KLK 6、ADAM 29、LGAL 4、TSPAN 8和SHPS-1的表达在MUC 1下调的克隆和对照细胞之间被发现显著不同。体内试验表明，与注射对照细胞的小鼠相比，注射MUC 1下调细胞的小鼠产生更小的肿瘤。这些结果表明，MUC 1下调改变了MKN 45胃癌细胞的表型和致瘤性，以及可能参与致瘤事件的几种分子的表达。因此，MUC 1应进一步研究，以更好地阐明其作为胃癌治疗新靶点的潜力。
Gastric carcinoma is the second leading cause of cancer-associated death worldwide. The high mortality associated with this disease is in part due to limited knowledge about gastric carcinogenesis and a lack of available therapeutic and prevention strategies. MUC1 is a high molecular weight transmembrane mucin protein expressed at the apical surface of most glandular epithelial cells and a major component of the mucus layer above gastric mucosa. Overexpression of MUC1 is found in approximately 95% of human adenocarcinomas, where it is associated with oncogenic activity. The role of MUC1 in gastric cancer progression remains to be clarified. We downregulated MUC1 expression in a gastric carcinoma cell line by RNA interference and studied the effects on cellular proliferation (MTT assay), apoptosis (TUNEL assay), migration (migration assay), invasion (invasion assay) and aggregation (aggregation assay). Global gene expression was evaluated by microarray analysis to identify alterations that are regulated by MUC1 expression. In vivo assays were also performed in mice, in order to study the tumorigenicity of cells with and without MUC1 downregulation in MKN45 gastric carcinoma cell line. Downregulation of MUC1 expression increased proliferation and apoptosis as compared to controls, whereas cell-cell aggregation was decreased. No significant differences were found in terms of migration and invasion between the downregulated clones and the controls. Expression of TCN1, KLK6, ADAM29, LGAL4, TSPAN8 and SHPS-1 was found to be significantly different between MUC1 downregulated clones and the control cells. In vivo assays have shown that mice injected with MUC1 downregulated cells develop smaller tumours when compared to mice injected with the control cells. These results indicate that MUC1 downregulation alters the phenotype and tumorigenicity of MKN45 gastric carcinoma cells and also the expression of several molecules that can be involved in tumorigenic events. Therefore, MUC1 should be further studied to better clarify its potential as a novel therapeutic target for gastric cancer.
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影响因子：
11.2
作者：
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