Reg IV is a direct target of intestinal transcriptional factor CDX2 in gastric cancer.
Reg IV is a direct target of intestinal transcriptional factor CDX2 in gastric cancer.
复制标题
DOI：
10.1371/journal.pone.0047545
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Yasui W
中科院分区：
文献类型：
--
作者：
Naito Y;Oue N;Hinoi T;Sakamoto N;Sentani K;Ohdan H;Yanagihara K;Sasaki H;Yasui W
REG 4编码Reg IV蛋白，是钙依赖性凝集素超家族的成员，是表皮生长因子受体/Akt/激活蛋白-1信号通路的有效激活剂。几种人类癌症过表达Reg IV，并且Reg IV表达与肠表型分化相关。然而，REG 4转录的调控仍不清楚。在本研究中，我们研究了CDX 2是否调节胃癌（GC）细胞中Reg IV的表达。采用Western blot和定量逆转录-聚合酶链反应（RT-PCR）检测9株胃癌细胞系和2株结肠癌细胞系中Reg IV和CDX 2的表达。用荧光素酶法检测REG 4基因5′端侧翼区的功能。在9个GC细胞系中，内源性Reg IV和CDX 2表达具有良好的相关性。使用雌激素受体调节形式的CDX 2，在HT-29细胞中观察到Reg IV表达的快速诱导。报告基因分析揭示了REG 4基因5′-侧翼区共有CDX 2 DNA结合元件在转录中的重要作用。染色质免疫沉淀试验表明，CDX 2直接与REG 4的5′-侧翼区结合。这些结果表明，CDX 2蛋白直接调节Reg IV表达。
REG4, which encodes Reg IV protein, is a member of the calcium-dependent lectin superfamily and potent activator of the epidermal growth factor receptor/Akt/activator protein-1 signaling pathway. Several human cancers overexpress Reg IV, and Reg IV expression is associated with intestinal phenotype differentiation. However, regulation of REG4 transcription remains unclear. In the present study, we investigated whether CDX2 regulates Reg IV expression in gastric cancer (GC) cells. Expression of Reg IV and CDX2 was analyzed by Western blot and quantitative reverse transcription–polymerase chain reaction in 9 GC cell lines and 2 colon cancer cell lines. The function of the 5′-flanking region of the REG4 gene was characterized by luciferase assay. In 9 GC cell lines, endogenous Reg IV and CDX2 expression were well correlated. Using an estrogen receptor-regulated form of CDX2, rapid induction of Reg IV expression was observed in HT-29 cells. Reporter gene assays revealed an important role in transcription for consensus CDX2 DNA binding elements in the 5′-flanking region of the REG4 gene. Chromatin immunoprecipitation assays showed that CDX2 binds directly to the 5′-flanking region of REG4. These results indicate that CDX2 protein directly regulates Reg IV expression.
登录
查看更多内容
影响因子：
29.4
作者：
Bishnupuri, KS;Luo, QZ;Dieckgraefe, BK
通讯作者：
Dieckgraefe, BK
影响因子：
29.4
作者：
Hinoi, T;Lucas, PC;Fearon, ER
通讯作者：
Fearon, ER
影响因子：
3.7
作者：
Mossman D;Scott RJ
通讯作者：
Scott RJ
影响因子：
7.3
作者：
Oue, N;Mitani, Y;Yasui, W
通讯作者：
Yasui, W
影响因子：
7
作者：
Gibson, UEM;Heid, CA;Williams, PM
通讯作者：
Williams, PM