The transcription factor ZEB1 promotes chemoresistance in prostate cancer cell lines

ASIAN JOURNAL OF ANDROLOGY

dc.creatorOrellana-Serradell, Octavio Andrés
dc.creatorHerrera-Ramírez, Daniela Francisca
dc.creatorCastellón, Enrique A
dc.creatorContreras-Muñoz, Héctor Ruberly
dc.date2021-08-23T22:55:31Z
dc.date2022-07-07T02:32:47Z
dc.date2021-08-23T22:55:31Z
dc.date2022-07-07T02:32:47Z
dc.date2019
dc.date.accessioned2023-08-22T22:31:04Z
dc.date.available2023-08-22T22:31:04Z
dc.identifier1151214
dc.identifier1151214
dc.identifierhttps://hdl.handle.net/10533/251644
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8347275
dc.descriptionOne of the factors promoting tumoral progress is the abnormal activation of the epithelial-mesenchymal transition (EMT) program which has been associated with chemoresistance in tumoral cells. The transcription factor zinc finger E-box-binding homeobox 1 (ZEB1), a key EMT activator, has recently been related to docetaxel resistance, the main chemotherapeutic used in advanced prostate cancer treatment. The mechanisms involved in this protective effect are still unclear. In a previous work, we demonstrated that ZEB1 expression induced an EMT-like phenotype in prostate cancer cell lines. In this work, we used prostate cancer cell lines 22Rv1 and DU145 to study the effect of ZEB1 modulation on docetaxel resistance and its possible mechanisms. The results showed that ZEB1 overexpression conferred to 22Rv1 cell resistance to docetaxel while its silencing made DU145 cells more sensitive to it. Analysis of resistance markers showed no presence of ATP-binding cassette subfamily B member 1 (MDR1) and no changes in breast cancer resistance protein (BCRP) or ATP-binding cassette subfamily C member 10 (MRP7). However, a correlation between ZEB1, multidrug resistance-associated protein 1 (MRP1), and ATP-binding cassette subfamily C member 4 (MRP4) expression was observed. MRP4 inhibition, using MK571, resensitized cells with ZEB1 overexpression to docetaxel treatment. In addition, modulation of ZEB1 and subsequent change in MRP4 expression correlated with a lower apoptotic response to docetaxel, characterized by lower B-cell lymphoma 2 (Bcl2), high BCL2-associated X protein (Bax), and high active caspase 3 expression. The response to docetaxel in our model seems to be mediated mainly by activation of the apoptotic death program. Our results showed that modulation of MRP4 could be a mediator of ZEB1-related resistance to docetaxel in prostate cancer, making it a possible marker for chemotherapy response in patients who do not express MDR1.
dc.descriptionRegular 2015
dc.descriptionFONDECYT
dc.descriptionFONDECYT
dc.languageeng
dc.relationhandle/10533/111557
dc.relationhandle/10533/111541
dc.relationhandle/10533/108045
dc.relationhttps://doi.org/10.4103/aja.aja_1_19
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.rightsinfo:eu-repo/semantics/article
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleThe transcription factor ZEB1 promotes chemoresistance in prostate cancer cell lines
dc.titleASIAN JOURNAL OF ANDROLOGY
dc.typeArticulo
dc.typeinfo:eu-repo/semantics/publishedVersion


Este ítem pertenece a la siguiente institución