Elucidation of mechanisms of pancreatic oncogenesis and establishment of novel therapy by modulating Notch signaling

阐明胰腺肿瘤发生机制并通过调节 Notch 信号建立新疗法

• 批准号: 15590615
• 负责人: KIMURA Kenji
• 金额: $ 2.24万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590615/
• 关键词: mouse pancreatic cancer model; Notch; 膵癌; マウス膵発癌モデル

[Background]Although it is reported that Notch signaling is activated in various cancer cells, the role of Notch signaling at early stage of oncogenesis in pancreas.[Aim]To establish novel mouse pancreatic cancer model using green mouse.To investigate the role of Notch signaling on pancreatic oncogenesis.[Results]1)Notch1 was expressed from PanIN-1A to invasive carcinoma.2)Tubular complex was detected in pancreas two weeks after DMBA injection. PanIN-2 lesion was observed in pancreas one month after DMBA injection. Invasive carcinoma occurred more than two months after DMBA injection. Tumor cells were CK-positive, vimentin-negative.3)Smad4 was downregulated in invasive carcinoma. CyclinD1 and p53 were upregulated in invasive carcinoma.4)Notch1 mRNA was upregulated in PanIN lesion and Invasive carcinoma. PDx1 mRNA was upregulated in PanIN lesion and Invasive carcinoma.[Conculusions]We established novel mouse pancreatic cancer model. Notch signaling was upregulated at early stage of oncogenesis. Notch inhibits differentiation in pancreatic cancer cells.

【背景】虽然有报道Notch信号在多种癌细胞中被激活，但Notch信号在胰腺肿瘤发生早期的作用尚不清楚。[目的]利用绿色小鼠建立新型小鼠胰腺癌模型。探讨Notch信号在胰腺肿瘤发生中的作用。【结果】1)PanIN-1A在浸润性癌中表达Notch1。2)注射DMBA后2周胰腺检测到管状复合体。注射DMBA 1个月后观察胰腺PanIN-2病变。注射DMBA后2个月以上发生浸润性癌。肿瘤细胞ck阳性，vimentin阴性。3)Smad4在侵袭性癌中表达下调。CyclinD1和p53在浸润性癌中表达上调。4) PanIN病变和浸润性癌中Notch1 mRNA表达上调。PDx1 mRNA在PanIN病变和浸润性癌中表达上调。【结论】建立了新型小鼠胰腺癌模型。Notch信号在肿瘤发生早期被上调。Notch抑制胰腺癌细胞的分化。

项目成果

The Role of Notch Signaling Pathway in Pancreatic Cancer Cells

Notch信号通路在胰腺癌细胞中的作用

• 发表时间: 2004
• 期刊: Pancreatology 4・3
• 作者: Kimura K;Satoh K;Hamada S;Shimosegawa T
• 通讯作者: Shimosegawa T

4-hydroxy-2,3-nonenal activates activator protein-1 and mitogen-activated protein kinases in rat pancreatic stellate cells.

4-羟基-2,3-nonenal 激活大鼠胰腺星状细胞中的激活蛋白-1 和丝裂原激活蛋白激酶。

• 发表时间: 2004
• 期刊: World J of Gastroenterology 10・16
• 作者: Kikuta K;Masamune A;Satoh M;Suzuki N;Shimosegawa T
• 通讯作者: Shimosegawa T

MSX2 Enhances Malignant Phenotype of Human Pancreatic Cancer Cell Line BxPC-3

MSX2 增强人胰腺癌细胞系 BxPC-3 的恶性表型

• 发表时间: 2004
• 期刊: Pancreatology 4・3
• 作者: Satoh K;Hamada S;Kimura K;Shimosegawa T
• 通讯作者: Shimosegawa T

Hereditary pancreatitis as the premalignant disease : a Japanese case of pancreatic cancer involving the SPINK1 gene mutation N34S.

遗传性胰腺炎作为癌前疾病：日本一例涉及 SPINK1 基因突变 N34S 的胰腺癌。

• 发表时间: 2004
• 期刊: Pancreas 28・3
• 作者: Masamune A;Mizutamari H;Kume K;Satoh K;Shimosegawa T
• 通讯作者: Shimosegawa T

Sakai Y. et al.: "Macrophage migration inhibitory factor is a critical mediator of severe acute pancreatitis"Gastroenterology. 124. 725-726 (2003)

Sakai Y.等人：“巨噬细胞迁移抑制因子是重症急性胰腺炎的关键介质”胃肠病学。