Molecular mechanism of the PPARγ ligand-induced growth arrest in GI cancers

PPARγ配体诱导胃肠癌生长停滞的分子机制

• 批准号: 18590666
• 负责人: OKUMURA Toshikatsu
• 金额: $ 2.49万
• 依托单位: Asahikawa Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590666/
• 关键词: PPARgamma; troglitazone; E-cadherin; claudin; cell invasion; MEK-ERK signal; Pancreas cancer; 抗腫瘍作用

We reported that thiazolidinediones, PPARgamma ligands, induce growth arrest, apoptosis and inhibit cell invasion in gastrointestinal cancer cells including human pancreatic cancer cells. A series of studies demonstrated that accumulation of p27 and inhibition of MEK-ERK signaling play a role in the inhibition of cell growth by PPARgamma lignads. Because E-cadherin and tight junction (TJ) proteins are known as molecules that are involved in cell growth and cell motility, we have examined in this study the effect of PPARgamma ligand on the expression of E-cadherin and TJ proteins in human pancreatic cancer cells, PK-1. Troglitazone dose-dependently up-regulated the expression of E-cadherin and claudin-4 mRNAs and proteins. MEK-ERK inhibition by PD98059 or U0126 increased expression of E-cadherin and claudin-4, and inhibited cell invasion. Since we have shown that troglitazone blocks MER-ERK signaling in PK-l cells, all these results suggest that troglitazone inhibits MEK-ERK signaling, followed by induction of E-cadherin and claudin-4, thereby inhibiting cell invasion in human pancreatic cancer cells.

我们报道了噻唑烷二酮类PPAR-γ配体能诱导胃肠道癌细胞包括人胰腺癌细胞的生长停滞、凋亡和抑制细胞侵袭。一系列研究表明，p27的积聚和MEK-ERK信号通路的抑制在PPAR-Gamma木脂素抑制细胞生长中起作用。由于E-钙粘蛋白和紧密连接(TJ)蛋白是已知的与细胞生长和细胞运动有关的分子，我们在本研究中检测了PPARγ配体对人胰腺癌细胞PK-1中E-钙粘蛋白和TJ蛋白表达的影响。曲格列酮呈剂量依赖性上调E-钙粘蛋白和claudin-4mRNAs及蛋白的表达。PD98059或U0126抑制MEK-ERK使E-钙粘蛋白和claudin-4表达增加，并抑制细胞侵袭。由于我们已发现曲格列酮阻断PK-L细胞中的mer-ERK信号转导，所有这些结果表明，曲格列酮可抑制MERK-ERK信号转导，进而诱导E-钙粘蛋白和claudin-4的表达，从而抑制人胰腺癌细胞的侵袭。

项目成果

Up-regulation of ADRP in fatty liver in human and liver steatosis in mice fed with high fat diet

• DOI: 10.1016/j.bbrc.2005.12.121
• 发表时间: 2006-02-24
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Motomura, W;Inoue, M;Okumura, T
• 通讯作者: Okumura, T

Gemcitabine chemoresistance and molecular markers associated with gemcitabine transport and metabolism in human pancreatic cancer cells.

• DOI: 10.1038/sj.bjc.6603559
• 发表时间: 2007-02-12
• 期刊: British journal of cancer
• 影响因子: 8.8

Tissue distribution of a collectin CL-K1 in murine tissues

小鼠组织中集合素 CL-K1 的组织分布

• 发表时间: 2008
• 期刊: Journal of Histchemistry. and Cytochemistry 56
• 作者: Motomura W;Yoshizaki T;Ohtani K;Okumura T;et.al.
• 通讯作者: et.al.