Reprogramming of cell junction modules during stepwise epithelial to mesenchymal transition and accumulation of malignant features in vitro in a prostate cell model |
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| Authors: | Ke Xi-song Li Wen-cheng Hovland Randi Qu Yi Liu Run-hui McCormack Emmet Thorsen Frits Olsen Jan Roger Molven Anders Kogan-Sakin Ira Rotter Varda Akslen Lars A Oyan Anne Margrete Kalland Karl-Henning |
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| Institution: | aThe Gade Institute, University of Bergen, Bergen, Norway;bDepartment of Microbiology, Haukeland, University Hospital, Bergen, Norway;cUrological Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, P.R. China;dCenter of Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway;eDepartment of Molecular Biology, University of Bergen, Bergen, Norway;fModern Research Center for Traditional Chinese Medicine, Second Military Medical University, Shanghai, P.R. China;gDepartment of Medicine, Haukeland University Hospital, Bergen, Norway;hDepartment of Biomedicine, University of Bergen, Bergen, Norway;iDepartment of Pathology, Haukeland University Hospital, Bergen, Norway;jDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel |
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| Abstract: | Epithelial to mesenchymal transition (EMT) is pivotal in tumor metastasis. Our previous work reported an EMT model based on primary prostate epithelial cells (EP156T) which gave rise to cells with mesenchymal phenotype (EPT1) without malignant transformation. To promote prostate cell transformation, cells were maintained in saturation density cultures to select for cells overriding quiescence. Foci formed repeatedly following around 8 weeks in confluent EPT1 monolayers. Only later passage EPT1, but not EP156T cells of any passage, could form foci. Cells isolated from the foci were named EPT2 and formed robust colonies in soft agar, a malignant feature present neither in EP156T nor in EPT1 cells. EPT2 cells showed additional malignant traits in vitro, including higher ability to proliferate following confluence, higher resistance to apoptosis and lower dependence on exogenous growth factors than EP156T and EPT1 cells. Microarray profiling identified gene sets, many of which belong to cell junction modules, that changed expression from EP156T to EPT1 cells and continued to change from EPT1 to EPT2 cells. Our findings provide a novel stepwise cell culture model in which EMT emerges independently of transformation and is associated with subsequent accumulation of malignant features in prostate cells. Reprogramming of cell junction modules is involved in both steps. |
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| Keywords: | Prostate Cell model EMT Malignant features Adhesion modules |
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