• Français
    • English
  • Français 
    • Français
    • English
  • Login
View Document 
  •   Savoirs UdeS Home
  • Médecine et sciences de la santé
  • Publications et recherches – Médecine et sciences de la santé
  • Médecine et sciences de la santé – Articles de périodiques
  • View Document
  •   Savoirs UdeS Home
  • Médecine et sciences de la santé
  • Publications et recherches – Médecine et sciences de la santé
  • Médecine et sciences de la santé – Articles de périodiques
  • View Document
JavaScript is disabled for your browser. Some features of this site may not work without it.

Browse

All of Savoirs UdeSDomains & CollectionsBy Issue DateAuthorsTitlesSubjectsDirectorsThis CollectionBy Issue DateAuthorsTitlesSubjectsDirectors

My Account

Login

Statistics

View Usage Statistics

Induction by estrogens of methotrexate resistance in MCF-7 breast cancer cells

Thumbnail
View/Open
Article (223.5Kb)
Publication date
1998
Author(s)
Thibodeau, Paul A.; Bissonnette, Nathalie; Kocsis-Bédard, Suzanne; Hunting, Darel; Paquette, Benoit
Editor(s)
Université de Sherbrooke. Département de radiobiologie
Subject
Development of drug resistance limites the effectiveness of chemotherapy treatments
Show full document record
Abstract
Development 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.
URI
http://hdl.handle.net/11143/6762
Collection
  • Médecine et sciences de la santé – Articles de périodiques [222]

DSpace software [version 5.4 XMLUI], copyright © 2002-2015  DuraSpace
Contact Us | Send Feedback
 

 


DSpace software [version 5.4 XMLUI], copyright © 2002-2015  DuraSpace
Contact Us | Send Feedback