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Transgenic introduction of androgen receptor into estrogen-receptor-, progesterone-receptor-, and androgen-receptor-negative breast cancer cells renders them responsive to hormonal manipulation.

AbstractBACKGROUND:
Estrogen-receptor (ER)-, progesterone-receptor (PR)-, and androgen-receptor (AR)-negative breast cancer cells are unaffected by treatment with dehydroepiandrosterone-sulfate (DHEAS) and an aromatase inhibitor (AI). We hypothesized that cell growth would be inhibited with DHEAS/AI treatment after successful transfection of an AR expression vector.
METHODS:
ER/PR/AR-negative breast cancer cells were transfected with an AR expression vector and treated with DHEAS/AI for 2 days. Growth inhibition of these cells was compared with that of transfected cells treated with only AI or with nontransfected cells treated with DHEAS/AI. Mann-Whitney U test was used to determine statistical significance.
RESULTS:
Cell death rates of 53.5% (P = .001) and 40.1% (P = .006) were seen in transfected cells treated with DHEAS/AI compared with controls for days 1 and 2, respectively. Nontransfected cells were unaffected by treatment.
COMMENTS:
ER/PR/AR-negative cells transfected with AR were killed by DHEAS/AI treatment, providing evidence that AR is responsible for this effect. This provides the first AR-targeted hormonal therapy for ER breast cancer.
AuthorsJennifer R Garreau, Patrick Muller, Rodney Pommier, Suellen Pommier
JournalAmerican journal of surgery (Am J Surg) Vol. 191 Issue 5 Pg. 576-80 (May 2006) ISSN: 0002-9610 [Print] United States
PMID16647340 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • RNA, Messenger
  • Receptors, Androgen
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Steryl-Sulfatase
Topics
  • Breast Neoplasms (drug therapy, metabolism, pathology)
  • Cell Death (drug effects, physiology)
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • In Vitro Techniques
  • RNA, Messenger (genetics)
  • Receptors, Androgen (genetics, metabolism)
  • Receptors, Estrogen (genetics, metabolism)
  • Receptors, Progesterone (genetics, metabolism)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Steryl-Sulfatase (therapeutic use)
  • Transfection
  • Tumor Cells, Cultured

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