c-Jun N terminal kinase modulates NOX-4 derived ROS production and myofibroblasts differentiation in human breast stromal cells

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dc.contributor.authorArancibia, Rodrigo.
dc.contributor.authorSmith, Patricio C.
dc.contributor.authorTobar, Nicolás.
dc.contributor.authorToyos, Marcela.
dc.contributor.authorUrra, Carla.
dc.contributor.authorMéndez, Nicolás.
dc.contributor.authorMartínez, Jorge.
dc.date.accessioned2019-10-17T13:53:23Z
dc.date.available2019-10-17T13:53:23Z
dc.date.issued2014
dc.date.updated2019-10-14T18:35:30Z
dc.description.abstractAbstract Background Hard consistency, developed under the influence of tumor cell factors, is a characteristic feature of a breast tumor. Activation of resident fibroblasts leading to a myofibroblast phenotype is the principal feature that orchestrates this fibrotic process. The aim of this study was to assess the effects induced by TGF-β1, a growth factor abundantly present in tumor microenvironment, on the molecular mechanisms that mediate myofibroblastic differentiation of normal human mammary fibroblasts. Methods We used an immortalized fibroblastic cell line derived from normal mammary tissue (RMF-EG cells) to study the effect of TGF-β1 in the expression of α-SMA and CTGF as markers of myofibroblastic differentiation. The influence of redox status and JNK activity on TGF-β1-induced transcriptional activity was measured by a luciferase reporter assay. We also used a shRNA approach to evaluate the influence of NOX4 in myofibroblastic differentiation. Results TGF-β1 stimulates the expression of myofibroblast markers α-SMA and CTGF. Using a NOX inhibitor (DPI) and cells expressing a shRNA for NOX4, we demonstrated that TGF-β1 promotes an oxidative environment that favors myofibroblastic differentiation. We also found that activation of c-Jun N-terminal kinase is required for TGF-β1-dependent expression of CTGF, NOX4 and α-SMA. Conclusions Human mammary stromal fibrosis, evaluated by the expression of early and late markers as CTGF and α-SMA, depends on the activation of JNK signaling pathway. Our results show that JNK activation is an early event that precedes the increase in ROS levels leading to myofibroblastic differentiation and tumor fibrosis, suggesting that inhibition of JNK may be used a method to interrupt the development of tumor desmoplasia.
dc.fuente.origenBiomed Central
dc.identifier.citationBMC Cancer. 2014 Aug 30;14(1):640
dc.identifier.doi10.1186/1471-2407-14-640
dc.identifier.urihttps://doi.org/10.1186/1471-2407-14-640
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/26655
dc.issue.numeroNo. 640
dc.language.isoen
dc.pagina.final10
dc.pagina.inicio1
dc.revistaBMC Canceres_ES
dc.rights.holderTobar et al.; licensee BioMed Central Ltd.
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.otherGlándulas mamariases_ES
dc.subject.otherFibrosises_ES
dc.subject.otherTumoreses_ES
dc.titlec-Jun N terminal kinase modulates NOX-4 derived ROS production and myofibroblasts differentiation in human breast stromal cellses_ES
dc.typeartículo
dc.volumenVol. 14
sipa.codpersvinculados1006488
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