Reprogramming of cell junction modules during stepwise epithelial to mesenchymal transition and accumulation of malignant features in vitro in a prostate cell model.
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.
The Gade Institute, University of Bergen, Bergen, Norway. Xisong.Ke@gades.uib.no
Xi-song
XS
Ke
Wen-cheng
WC
Li
Randi
R
Hovland
Yi
Y
Qu
Run-hui
RH
Liu
Emmet
E
McCormack
Frits
F
Thorsen
Jan Roger
JR
Olsen
Anders
A
Molven
Ira
I
Kogan-Sakin
Varda
V
Rotter
Lars A
LA
Akslen
Anne Margrete
AM
Oyan
Karl-Henning
KH
Kalland
D017209:Apoptosis; D018929:Cell Culture Techniques; D054337:Cell Dedifferentiation; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D002999:Clone Cells; D004847:Epithelial Cells / Q000166:cytology* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D020869:Gene Expression Profiling; D006801:Humans; D007365:Intercellular Junctions / Q000473:pathology*; D007621:Karyotyping; D008297:Male; D018895:Microsatellite Repeats; D011467:Prostate / Q000166:cytology* / Q000378:metabolism / Q000473:pathology