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dc.contributor.authorThibodeau, Paul A.fr
dc.contributor.authorBissonnette, Nathaliefr
dc.contributor.authorKocsis-Bédard, Suzannefr
dc.contributor.authorHunting, Darelfr
dc.contributor.authorPaquette, Benoitfr
dc.contributor.editorUniversité de Sherbrooke. Département de radiobiologiefr
dc.date.accessioned2015-04-29T00:02:09Z
dc.date.available2015-04-29T00:02:09Z
dc.date.created1998fr
dc.date.issued2015-04-28
dc.identifier.urihttp://hdl.handle.net/11143/6762
dc.description.abstractDevelopment of drug resistance is a major factor that limits the effectiveness of chemotherapy treatments. In this study, we determined whether estradiol or its metabolites 2-, 4- and 16[alpha]-hydroxyestrone could enhance the development of methotrexate resistance in the breast carcinoma cell line, MCF-7. Cells were incubated with the estrogens at a concentration of 10[superscript]–8 M for 12 cell doublings and enhancement of methotrexate resistance was measured with the Luria–Delbrück assay. The most efficient estrogens were the 4-hydroxyestrone and 16[alpha]-hydroxyestrone, which both stimulated methotrexate resistance by 88-fold as compared with the control without estrogen. 2-Hydroxyestrone had an enhancement factor of 33-fold, whereas estradiol showed a slight effect with an enhancement factor of 3.2- fold. To determine whether the estrogen receptor was involved in the development of resistance, expression of the pS2 gene, which contains an estrogen-responsive element, was measured. Both estradiol and 16[alpha]-hydroxyestrone stimulated expression of the pS2 gene. In contrast, 2- and 4-hydroxyestrone did not increase the level of pS2 mRNA. This suggests that tumors classified as estrogen receptor negative could also develop methotrexate resistance as the result of exposure to estrogens. The status of the tumor suppressor gene p53 was analyzed in methotrexate sensitive and resistant clones. In all the methotrexate resistant clones analyzed, the western blots indicated that the p53 protein was still present and transcriptionally competent, as measured by its capacity to stimulate transcription of the p21[superscript waf1/cip1] gene following UVB irradiation. However, the basal level of p53 was higher in resistant clones and addition of 2- or 4-hydroxyestrone increased p53 to levels equivalent to those observed following UVB irradiation. However, this induction of p53 accumulation by estrogens failed to stimulate the transcription of p21[superscript waf1/cip1], which indicates that a transcriptionally inactive form of p53 accumulated in methotrexate resistant cells.fr
dc.language.isoengfr
dc.relation.isformatofhttp://carcin.oxfordjournals.org/content/19/9/1545.full.pdffr
dc.relation.ispartofISSN:0143-3334fr
dc.relation.ispartofCarcinogenesis: integrative cancer researchfr
dc.subjectDevelopment of drug resistance limites the effectiveness of chemotherapy treatmentsfr
dc.titleInduction by estrogens of methotrexate resistance in MCF-7 breast cancer cellsfr
dc.typeArticlefr
udes.description.typestatusPost-publicationfr
udes.description.typepubRévisé et accepté par des pairsfr
udes.description.pages1545–1552fr
udes.description.period19 (9)fr
udes.description.diffusionDiffusé par Savoirs UdeS, le dépôt institutionnel de l'Université de Sherbrookefr
udes.description.sourceCarcinogenesis: integrative cancer researchfr
udes.autorisation.depottruefr
udes.description.ordreauteursThibodeau, Paul A.; Bissonnette, Nathalie; Kocsis-Bédard, Suzanne; Hunting, Darel; Paquette, Benoit


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