Analysis of the cell growth mechanism by ZIC2 transcription factor in pancreatic cancer cells.

ZIC2转录因子对胰腺癌细胞生长机制的分析

• 批准号: 23790424
• 负责人: INAGUMA Shingo
• 金额: $ 2.25万
• 依托单位: Aichi Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23790424/
• 关键词: ヘッジホッグ; 膵臓癌; ZIC2; アポトーシス; 細胞増殖; 転写因子

ZIC2 is one of five members of ZIC family gene those are indispensable for the development of central nervous system. Recently, we uncovered that ZIC2 is a unique member which is expressed in all (11/11) of the pancreatic ductal adenocarcinoma (PDAC) cell lines we tested.From the cDNA expression microarray analysis, we identified ANXA8 and FGFR3 as ZIC2 transcriptional targets. Furthermore, we uncovered that forced expression of ANXA8 reduced the apoptotic cell death of the ZIC2-knockdown PDAC cells and that ZIC2 accelerated ERK phosphorylation in FGFR3 dependent manner. Although ZIC2, ANXA8 and FGFR3 expressions were immunohistochemically under-detectable levels in the normal pancreatic duct, their expression was prominent in PanIN and PDAC cells.Our in vitro and in vivo experimental results indicate that ZIC2-ANXA8 and ZIC2-FGFR3-ERK axis are important signaling pathways for the regulation of apoptosis and cell proliferation in the PDAC development.

ZIC2是ZIC家族基因的五个成员之一，对于中枢神经系统的发育至关重要。最近，我们发现ZIC2是一个独特的成员，在我们测试的所有（11/11）胰腺导管腺癌（PDAC）细胞系中表达。通过cDNA表达微阵列分析，我们确定ANXA8和FGFR3为ZIC2转录靶点。此外，我们发现ANXA8的强制表达减少了ZIC2敲低的PDAC细胞的凋亡细胞死亡，并且ZIC2以FGFR3依赖性方式加速ERK磷酸化。尽管 ZIC2、ANXA8 和 FGFR3 在正常胰管中的表达在免疫组织化学上检测不到，但它们在 PanIN 和 PDAC 细胞中的表达却很突出。我们的体外和体内实验结果表明，ZIC2-ANXA8 和 ZIC2-FGFR3-ERK 轴是PDAC 发育过程中调节细胞凋亡和细胞增殖的重要信号通路。

项目成果

ヘッジホッグシグナル系転写因子ZIC2はFGFR3, ANXA8L2発現誘導を介して膵発がんを促進する

Hedgehog信号转录因子ZIC2通过诱导FGFR3和ANXA8L2表达促进胰腺癌发生

• 发表时间: 2014
• 作者: 稲熊真悟;ら
• 通讯作者: ら

ヘッジホッグシグナル系転写因子ZIC2はFGFR3, ANXA8L2発現誘導を介して膵発癌を促進する

Hedgehog信号转录因子ZIC2通过诱导FGFR3和ANXA8L2表达促进胰腺癌发生

• 发表时间: 2014
• 作者: 稲熊真悟;笠井謙次;橋本光義;陸美穂;池田洋
• 通讯作者: 池田洋

ZIC2 is an indispensable transcription factor for the cell growth of pancreatic ductal adenocarcinoma.

ZIC2是胰腺导管腺癌细胞生长不可缺少的转录因子。

• 发表时间: 2014
• 作者: Shingo Inaguma;Kenji Kasai;Mitsuyoshi Hashimoto;Miho Riku;Hiroshi Ikeda.
• 通讯作者: Hiroshi Ikeda.

GLI1 Modulates EMT in Pancreatic Cancer-Letter

• DOI: 10.1158/0008-5472.can-12-0379
• 发表时间: 2012-07-15
• 期刊: CANCER RESEARCH
• 影响因子: 11.2
• 作者: Inaguma, Shingo;Kasai, Kenji;Ikeda, Hiroshi
• 通讯作者: Ikeda, Hiroshi

ZIC2 is an indispensable transcription factor for the cell growth of pancreatic ductal adenocarcinoma

ZIC2是胰腺导管腺癌细胞生长不可缺少的转录因子

• 发表时间: 2014
• 作者: Shingo INAGUMA;et.al
• 通讯作者: et.al