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JDP2 和 ATF2 对人胰腺癌细胞系上皮-间充质转化的影响。

The effect of JDP2 and ATF2 on the epithelial-mesenchymal transition of human pancreatic cancer cell lines.

机构信息

Department of Pancreatic Gastroenterologic Surgery, First Hospital of China Medical University, No 92, Nanjing Rd, Shenyang 110001, China.

出版信息

Pathol Oncol Res. 2012 Jul;18(3):571-7. doi: 10.1007/s12253-011-9476-6. Epub 2011 Nov 23.

Abstract

Pancreatic cancer is a common malignancy with a bleak outcome due to the early occurrence of micro-metastases and poor prognosis. The epithelial-mesenchymal transition (EMT) is considered to be related to the invasion and metastasis of a variety of malignant tumors. Currently, there is no research regarding the relationship of pancreatic cancer EMT with Jun dimerization protein 2 (JDP2), an inhibitor of the activator protein-1 (AP-1) family, and activating transcription factor-2 (ATF2), an AP-1-family member. In this study, we used western blot analysis and immunofluorescence to detect the protein expression of the epithelial marker E-cadherin and the mesenchymal marker vimentin in the pancreatic cancer cell line BxPC3, which was transfected with JDP2 and induced by Collagen I. Compared with the negative control, the E-cadherin and vimentin expression levels did not change significantly, whereas E-cadherin expression decreased and vimentin expression increased in the control group transfected with empty plasmid, suggesting that JDP2 inhibits the EMT induced by Collagen I. Additionally, we verified that compared with the negative control, the morphology of the Capan2 cell line induced by TGF-β1 after transfection with ATF2 was significantly changed, as was the mRNA expression of E-cadherin, whereas the mRNA expression of vimentin, Snail, and ATF2 was significantly increased. Cell invasiveness was also significantly increased (P < 0.01), suggesting that ATF2, together with TGF-β1, induced EMT in the Capan2 cell line. The members of the AP-1 family are closely related to EMT and that JDP2, as an AP-1-family inhibitor, inhibits EMT, which could lead to a new direction in molecular-targeted therapy for pancreatic cancer.

摘要

胰腺癌是一种常见的恶性肿瘤,由于微转移的早期发生和预后不良,导致其结局惨淡。上皮-间充质转化(EMT)被认为与多种恶性肿瘤的侵袭和转移有关。目前,尚无研究探讨胰腺癌细胞 EMT 与 Jun 二聚化蛋白 2(JDP2)的关系,JDP2 是激活蛋白-1(AP-1)家族的抑制剂,而激活转录因子-2(ATF2)是 AP-1 家族的成员。在这项研究中,我们使用 Western blot 分析和免疫荧光检测了转染 JDP2 并经胶原 I 诱导的胰腺癌细胞系 BxPC3 中上皮标志物 E-钙黏蛋白和间充质标志物波形蛋白的蛋白表达。与阴性对照相比,E-钙黏蛋白和波形蛋白的表达水平没有明显变化,而转染空质粒的对照组 E-钙黏蛋白表达降低,波形蛋白表达增加,表明 JDP2 抑制胶原 I 诱导的 EMT。此外,我们验证了与阴性对照相比,转染 ATF2 后 TGF-β1 诱导的 Capan2 细胞系形态明显改变,E-钙黏蛋白的 mRNA 表达降低,而波形蛋白、Snail 和 ATF2 的 mRNA 表达显著增加。细胞侵袭性也显著增加(P < 0.01),表明 ATF2 与 TGF-β1 共同诱导 Capan2 细胞系发生 EMT。AP-1 家族的成员与 EMT 密切相关,JDP2 作为 AP-1 家族的抑制剂,抑制 EMT,这可能为胰腺癌的分子靶向治疗开辟新的方向。

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