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Overexpression of S100A4 in human cancer cell lines resistant to methotrexate

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dc.creator Mencía Trinchant, Núria
dc.creator Selga i Coma, Elisabet
dc.creator Rico, Isabel
dc.creator Almagro García, Ma. Cristina de
dc.creator Villalobos Alberú, Xenia
dc.creator Ramírez, Sara
dc.creator Adan, Jaume
dc.creator Hernández, José Luis
dc.creator Noé Mata, Verónica
dc.creator Ciudad i Gómez, Carlos Julián
dc.date 2010-09-10T08:56:46Z
dc.date 2010-09-10T08:56:46Z
dc.date 2010-06-01
dc.date.accessioned 2024-12-16T10:25:12Z
dc.date.available 2024-12-16T10:25:12Z
dc.identifier 1471-2407
dc.identifier http://hdl.handle.net/2445/13643
dc.identifier 579912
dc.identifier 20515499
dc.identifier.uri http://fima-docencia.ub.edu:8080/xmlui/handle/123456789/18999
dc.description Background: Methotrexate is a chemotherapeutic drug that is used in therapy of a wide variety of cancers. The efficiency of treatment with this drug is compromised by the appearance of resistance. Combination treatments of MTX with other drugs that could modulate the expression of genes involved in MTX resistance would be an adequate strategy to prevent the development of this resistance. Methods: The differential expression pattern between sensitive and MTX-resistant cells was determined by whole human genome microarrays and analyzed with the GeneSpring GX software package. A global comparison of all the studied cell lines was performed in order to find out differentially expressed genes in the majority of the MTX-resistant cells. S100A4 mRNA and protein levels were determined by RT-Real-Time PCR and Western blot, respectively. Functional validations of S100A4 were performed either by transfection of an expression vector for S100A4 or a siRNA against S100A4. Transfection of an expression vector encoding for beta-catenin was used to inquire for the possible transcriptional regulation of S100A4 through the Wnt pathway. Results S100A4 is overexpressed in five out of the seven MTX-resistant cell lines studied. Ectopic overexpression of this gene in HT29 sensitive cells augmented both the intracellular and extracellular S100A4 protein levels and caused desensitization toward MTX. siRNA against S100A4 decreased the levels of this protein and caused a chemosensitization in combined treatments with MTX. beta-catenin overexpression experiments support a possible involvement of the Wnt signaling pathway in S100A4 transcriptional regulation in HT29 cells. Conclusions: S100A4 is overexpressed in many MTX-resistant cells. S100A4 overexpression decreases the sensitivity of HT29 colon cancer human cells to MTX, whereas its knockdown causes chemosensitization toward MTX. Both approaches highlight a role for S100A4 in MTX resistance.
dc.format 13 p.
dc.format application/pdf
dc.language eng
dc.publisher BioMed Central
dc.relation Reproducció del document publicat a: http://dx.doi.org/10.1186/1471-2407-10-250
dc.relation BMC Cancer 2010, 10:250, p. 1-13
dc.relation http://dx.doi.org/10.1186/1471-2407-10-250
dc.rights cc-by (c) Mencía et al., 2010.
dc.rights http://creativecommons.org/licenses/by/2.0/
dc.rights info:eu-repo/semantics/openAccess
dc.source Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
dc.subject Metotrexat
dc.subject Resistència als medicaments
dc.subject Cèl·lules canceroses
dc.subject Càncer
dc.subject Quimioteràpia
dc.subject Methotrexate
dc.subject Resistència als medicaments
dc.subject Cancer cells
dc.subject Cancer
dc.subject Chemotherapy
dc.title Overexpression of S100A4 in human cancer cell lines resistant to methotrexate
dc.type info:eu-repo/semantics/article
dc.type info:eu-repo/semantics/publishedVersion


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