Reprogramming of cell junction modules during stepwise epithelial to mesenchymal transition and accumulation of malignant features in vitro in a prostate cell model

Journal Article · Sat Jan 15 00:00:00 EST 2011 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2010.10.009· OSTI ID:22212087

Ke, Xi-song ^[1]; Li, Wen-cheng ^[1]; Hovland, Randi ^[2]; Qu, Yi ^[1]; Liu, Run-hui ^[3]; McCormack, Emmet ^[4]; Thorsen, Frits ^[5]; Olsen, Jan Roger ^[1]; Molven, Anders ^[1]; Kogan-Sakin, Ira; Rotter, Varda ^[6]; Akslen, Lars A. ^[1]; Oyan, Anne Margrete ^[1]; Kalland, Karl-Henning ^[1]

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1. The Gade Institute, University of Bergen, Bergen (Norway)
2. Center of Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen (Norway)
3. Modern Research Center for Traditional Chinese Medicine, Second Military Medical University, Shanghai (China)
4. Department of Medicine, Haukeland University Hospital, Bergen (Norway)
5. Department of Biomedicine, University of Bergen, Bergen (Norway)
6. Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot (Israel)

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.

• OSTI ID: 22212087
• Journal Information: Experimental Cell Research, Vol. 317, Issue 2; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADHESION
AGAR
APOPTOSIS
CELL CULTURES
CELL TRANSFORMATIONS
GENES
GROWTH FACTORS
IN VITRO
METASTASES
NEOPLASMS
PHENOTYPE
PROSTATE