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


CONCLUSIONS
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.
Garreau
Jennifer R
JR
Division of Surgical Oncology, Department of Surgery, Oregon Health and Sciences University, 3181 S. W. Sam Jackson Park Rd., L223A, Portland, OR 97201, USA.
Muller
Patrick
P
Pommier
Rodney
R
Pommier
Suellen
S
D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D012333:RNA, Messenger / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043266:Steryl-Sulfatase / Q000627:therapeutic use; D014162:Transfection; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D043266:Steryl-Sulfatase