CDX2 serves as a Wnt signaling inhibitor and is frequently methylated in lung cancer.
CDX2 serves as a Wnt signaling inhibitor and is frequently methylated in lung cancer.
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CDX2 作为 Wnt 信号传导抑制剂，在肺癌中经常被甲基化
DOI：
10.4161/cbt.21344
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发表时间：
2012-10
影响因子：
3.6
通讯作者：
Guo M
中科院分区：
文献类型：
--
作者：
Liu X;Zhang X;Zhan Q;Brock MV;Herman JG;Guo M
上游转录因子的异常启动子区高甲基化可能导致整个抗肿瘤基因网络的沉默。在这项研究中，我们探讨了转录因子编码基因，尾侧相关同源盒2 （CDX2）是否在肺癌启动子超甲基化中沉默，并研究了其潜在的肿瘤抑制功能。半定量RT-PCR结果显示，6株肺癌细胞系中有4株CDX2不表达或弱表达。CDX2的表达与CDX2启动子区甲基化状态相关，这是通过甲基化特异性PCR （MSP）和亚硫酸盐测序确定的。用去甲基化药物5-AZA -2′-脱氧胞苷（5-AZA）处理肺癌细胞株，诱导CDX2表达恢复。CDX2甲基化在人原发性肺癌中很常见（61 / 110,55.45%），而在正常肺组织中未发现甲基化。CDX2的重新表达抑制了肺癌细胞的增殖，阻断了G1期细胞。重表达CDX2可抑制β-catenin/TCF活性及下游基因表达，缺失CDX2可提高β-catenin/TCF活性及下游基因表达。综上所述，CDX2在肺癌中经常发生甲基化，CDX2的表达受启动子区超甲基化的调控。CDX2可能在肺癌中发挥抑瘤作用，通过抑制Wnt信号传导抑制肺癌细胞增殖。
Aberrant promoter region hypermethylation of upstream transcription factors may be responsible for silencing entire anti-neoplastic gene networks. In this study, we explored whether transcription factor coding gene, caudal-related homeobox 2 (CDX2), is silenced by promoter hypermethylation in lung cancer, and examined its potential tumor-suppressive functions. Semi-quantitative RT-PCR showed that four of six lung cancer cell lines exhibited no or weak CDX2 expression. Expression of CDX2 was correlated to CDX2 promoter region methylation status, as determined by methylation-specific PCR (MSP) and bisulfite sequencing. Restoration of CDX2 expression was induced by treatment with demethylating drug 5-aza-2'-deoxycytidine (5-AZA) in lung cancer cell lines. Methylation of CDX2 was common in human primary lung cancer (61 of 110 tumors, 55.45%), but no methylation was found in normal lung tissues. Re-expression of CDX2 suppressed lung cancer cell proliferation and blocked cells in G1 phase. β-catenin/TCF activity and downstream genes expression were inhibited by re-expression of CDX2, and increased by depletion of CDX2. In conclusion, CDX2 is frequently methylated in lung cancer, and expression of CDX2 is regulated by promoter region hypermethylation. CDX2 may serve as a tumor suppressor in lung cancer and inhibits lung cancer cell proliferation by suppressing Wnt signaling.
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DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
37.3
作者：
Tsou JA;Galler JS;Siegmund KD;Laird PW;Turla S;Cozen W;Hagen JA;Koss MN;Laird-Offringa IA
通讯作者：
Laird-Offringa IA
影响因子：
6.4
作者：
Guo, MingZhou;House, Michael G.;Herman, James G.
通讯作者：
Herman, James G.
影响因子：
30.8
作者：
Aoki, K;Tamai, Y;Taketo, MM
通讯作者：
Taketo, MM
影响因子：
11.2
作者：
Aoki, Koji;Kakizaki, Fumihiko;Taketo, Makoto M.
通讯作者：
Taketo, Makoto M.