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

Am J Surg. 2006 May;191(5):576-80. doi: 10.1016/j.amjsurg.2006.02.004.

Abstract

Background: 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.

Publication types

  • Comparative Study

MeSH terms

  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Death / drug effects
  • Cell Death / physiology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • In Vitro Techniques
  • RNA, Messenger / genetics*
  • Receptors, Androgen / genetics*
  • Receptors, Androgen / metabolism
  • Receptors, Estrogen / genetics*
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / genetics*
  • Receptors, Progesterone / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Steryl-Sulfatase / therapeutic use
  • Transfection
  • Tumor Cells, Cultured

Substances

  • RNA, Messenger
  • Receptors, Androgen
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Steryl-Sulfatase