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The study on the cross-talk between vitamin D and TGFβ signal transduction paihways in the pancreatic cancer cell lines

胰腺癌细胞株中维生素D与TGFβ信号转导通路的串扰研究

基本信息

批准号：
12670471
负责人：
KAWA Shigeyuki
金额：
$ 1.98万
依托单位：
Shinshu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670471/
关键词：
pancreatic cancer vitamin D TGFβ PPARγ troglitazone p21

项目摘要

1. The aim of die present study is to clarify whether the cross-talk between vitamin D and TGFβ signal Iransduclion pathways is operating in the pancreatic cancer cell lines. Pancreatic cancer cell line SUP-1, which well responds to both vitamin D and TGFβ, shows no expression of smad4 which acts at the terminal portion of TGFβ signal transduction pathways, suggesting that the cross-talk between vitamin D and TGFβ signal transduction pathways may be operating. However, no irancriptive activity of vitamin D receptor was observed in Die SUP-1 transfectecl by VDR response element after TGFβ treatment Accordingly, we cannot confirm he cross-talk between vitamin D and TGFβ signal transduction pathways.2. The aim of this study is to assess whether the PPARg ligand, troglilazone, inhibits' the growth of pancreatic cancer cells., Troglilazone, had growth inhibitory, and differentiation induction effects on die pancreatic ameer cell lines.through the up-expression of p21, suggesting a new molecular target for effective therapy against pancreatic cancer.3. Autoimmune pancreatitis is a distinctive disease entity characterized by high serum IgG4 concentrations, and we investigated the association between HLA alleles and autoimmune pancreatitis. The DRB1*0405-DQB1*0401 haplolype is significantly associated with autoimmune pancreatitis and may play a functional role in antigen presentation and the induction of an autoimmune response.

1.本研究的目的是阐明在胰腺癌细胞系中维生素D和TGFβ信号转导通路之间是否存在相互作用。胰腺癌细胞系P450 -1对维生素D和TGFβ都有很好的反应，但在TGFβ信号转导通路的末端部分没有显示出smad 4的表达，这表明维生素D和TGFβ信号转导通路之间可能存在串扰。然而，经TGFβ处理后，VDR反应元件转染的Die Ⅲ-1细胞中未观察到维生素D受体的转录活性，因此，我们不能证实维生素D与TGFβ信号转导通路之间存在相互作用.本研究的目的是评估PPARg配体troglilazone是否抑制胰腺癌细胞的生长，Troglilazone对胰腺癌细胞株具有生长抑制和诱导分化作用，通过上调p21的表达，提示其可能成为胰腺癌有效治疗的新的分子靶点.自身免疫性胰腺炎是一种独特的疾病实体，其特征是高血清IgG 4浓度，我们研究了HLA等位基因与自身免疫性胰腺炎之间的关联。DRB 1 *0405-DQB 1 *0401单倍型与自身免疫性胰腺炎显著相关，并且可能在抗原呈递和诱导自身免疫应答中发挥功能性作用。