4.4 Article

The Effect of JDP2 and ATF2 on the Epithelial-mesenchymal Transition of Human Pancreatic Cancer Cell Lines

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PATHOLOGY & ONCOLOGY RESEARCH
卷 18, 期 3, 页码 571-577

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SPRINGER
DOI: 10.1007/s12253-011-9476-6

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Pancreatic cancer; Epithelial-mesenchymal transition; Jun dimerization protein 2; Activator protein-1

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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-beta 1 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-beta 1, 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.

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