Metallothionein 1G functions as a tumor suppressor in thyroid cancer through modulating the PI3K/Akt signaling pathway.
Metallothionein 1G functions as a tumor suppressor in thyroid cancer through modulating the PI3K/Akt signaling pathway.
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金属硫蛋白 1G 通过调节 PI3K/Akt 信号通路作为甲状腺癌的肿瘤抑制因子
DOI：
10.1186/1471-2407-13-462
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发表时间：
2013-10-08
期刊：
影响因子：
3.8
通讯作者：
Hou P
中科院分区：
文献类型：
--
作者：
Fu J;Lv H;Guan H;Ma X;Ji M;He N;Shi B;Hou P
研究背景在甲状腺癌中有报道MT 1基因启动子甲基化介导的活化。然而，MT 1G在甲状腺癌发生中的作用仍不清楚。方法应用甲基化特异性PCR（Methylation specific PCR，MSP）技术检测甲状腺乳头状癌（papillary thyroid cancer，PTC）患者MT 1G基因启动子区甲基化状态及其与临床病理特征的关系。常规和实时定量RT-PCR测定用于评估mRNA表达。结果MT 1G在甲状腺癌细胞系中表达沉默或下调，在原发性甲状腺癌组织中的表达也明显低于正常甲状腺组织。启动子甲基化，沿着组蛋白修饰，在甲状腺肿瘤发生中促进MT 1 Gin活化。此外，我们的数据显示，MT 1G高甲基化与PTC患者的淋巴结转移显著正相关。重要的是，在甲状腺癌细胞中表达MT 1G显著抑制细胞生长和侵袭，结论MT 1G可能是甲状腺癌发生过程中的一种功能性肿瘤抑制剂，其作用机制主要是通过调节磷酸化肌醇3激酶（PI 3 K）/Akt通路，部分是通过调节Rb/Akt通路的活性。E2 F信号通路。
BackgroundMT1Ginactivation mediated by promoter methylation has been reported in thyroid cancer. However, the role ofMT1Gin thyroid carcinogenesis remains unclear. The aim of this study is to examine the biological functions and related molecular mechanisms ofMT1Gin thyroid cancer.MethodsMethylation-specific PCR (MSP) was performed to analyze promoter methylation ofMT1Gand its relationship with clinicopathological characteristics of papillary thyroid cancer (PTC) patients. Conventional and real-time quantitative RT-PCR assays were used to evaluate mRNA expression. The functions of ectopicMT1Gexpression were determined by cell proliferation and colony formation, cell cycle and apoptosis, as well as cell migration and invasion assays.ResultsMT1Gexpression was frequently silenced or down-regulated in thyroid cancer cell lines, and was also significantly decreased in primary thyroid cancer tissues compared with non-malignant thyroid tissues. Promoter methylation, along with histone modification, contributes toMT1Ginactivation in thyroid tumorigenesis. Moreover, our data showed thatMT1Ghypermethylation was significantly positively associated with lymph node metastasis in PTC patients. Importantly, restoringMT1Gexpression in thyroid cancer cells dramatically suppressed cell growth and invasiveness, and induced cell cycle arrest and apoptosis through inhibiting phosphorylation of Akt and Rb.ConclusionsWe have for the first time revealed thatMT1Gappears to be functional tumor suppressor involved in thyroid carcinogenesis mainly through modulating the phosphatidylinositol-3-kinase (PI3K)/Akt pathway and partially through regulating the activity of Rb/E2F pathway in this study.
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影响因子：
11.5
作者：
Hou, Peng;Liu, Dingxie;Xing, Mingzhao
通讯作者：
Xing, Mingzhao
DOI：
10.1016/j.bbrc.2010.08.018
发表时间：
2010-09-10
影响因子：
3.1
作者：
Kim, Tae Rim;Lee, Hee Min;Kim, In Gyu
通讯作者：
Kim, In Gyu
影响因子：
3.8
作者：
Henrique, R;Jerónimo, C;Sidransky, D
通讯作者：
Sidransky, D
影响因子：
3.5
作者：
Nevins, JR
通讯作者：
Nevins, JR
影响因子：
4.8
作者：
Ogawara, Y;Kishishita, S;Gotoh, Y
通讯作者：
Gotoh, Y