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Dehydroepiandrosterone sulfate causes proliferation of estrogen receptor-positive breast cancer cells despite treatment with fulvestrant.

AbstractHYPOTHESIS:
Dehydroepiandrosterone sulfate (DHEA-S) causes a proliferation of estrogen receptor (ER)-positive breast cancer cells, even with tamoxifen citrate blockade. The ER antagonist ICI 182780 (fulvestrant) will more effectively stop the proliferative effect of DHEA-S on breast cancer cells.
DESIGN:
Examination of in vitro breast cancer cell growth in the presence of fulvestrant and DHEA-S.
SETTING:
Surgical oncology research laboratory.
INTERVENTIONS:
The ER-positive and ER-negative breast cancer cells were pretreated with fulvestrant and stimulated with 900 microg/dL (22.8 micromol/L) of DHEA-S.
MAIN OUTCOME MEASURES:
Assays using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, thiazolyl blue, were performed on the third, fifth, and seventh days poststimulation and permitted the calculation of growth percent change.
RESULTS:
The ER-positive and progesterone receptor-positive cells demonstrated universal proliferation of 107% by day 7 when treated with fulvestrant, regardless of the dose. The ER-negative and progesterone receptor-negative cells demonstrated growth inhibition.
CONCLUSIONS:
The DHEA-S circumvented fulvestrant inhibition and caused ER-positive breast cancer cell growth.
AuthorsKristine E Calhoun, Rodney F Pommier, Patrick Muller, William S Fletcher, SuEllen Toth-Fejel
JournalArchives of surgery (Chicago, Ill. : 1960) (Arch Surg) Vol. 138 Issue 8 Pg. 879-83 (Aug 2003) ISSN: 0004-0010 [Print] United States
PMID12912747 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Estrogen Antagonists
  • Receptors, Estrogen
  • Fulvestrant
  • Estradiol
  • Dehydroepiandrosterone Sulfate
Topics
  • Breast Neoplasms (pathology)
  • Cell Division (drug effects)
  • Dehydroepiandrosterone Sulfate (pharmacology)
  • Estradiol (analogs & derivatives, pharmacology)
  • Estrogen Antagonists (pharmacology)
  • Female
  • Fulvestrant
  • Humans
  • In Vitro Techniques
  • Receptors, Estrogen (analysis)
  • Tumor Cells, Cultured (drug effects)

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