Estrogen and androgen receptors as comediators of breast cancer cell proliferation: providing a new therapeutic tool.
OBJECTIVE
Dehydroepiandrosterone sulfate (DHEA-S) comediates breast cancer progression via estrogen receptors (ERs) and androgen receptors (ARs).


METHODS
Breast cancer cells that were ER positive-AR positive or ER negative-AR positive were pretreated with anastrozole, tamoxifen citrate, or bicalutamide, then stimulated with 228 microM DHEA-S.


METHODS
University Surgical Oncology Research Laboratory.


METHODS
Receptor status was confirmed by reverse transcriptase polymerase chain reaction. Cellular activity was measured by a methylthiotetrazole proliferation assay in addition to ER nuclear translocation and mitogen-activated protein kinase activity by immunoassays.


RESULTS
The use of DHEA-S induced growth of 43.4% in ER-positive-AR-positive cells but inhibited ER-negative-AR-positive cells by 22%. Tamoxifen reduced growth of ER-positive-AR-positive cells to 8.9%. Bicalutamide restored normal growth of ER-negative-AR-positive cells. The ER nuclear translocation rate of 51% was reduced to 11% with tamoxifen. The use of DHEA-S induced mitogen-activated protein kinase by 5.4-fold.


CONCLUSIONS
Stimulation with DHEA-S induced proliferation through the ER but inhibited cells via the AR. Therapeutic comediation of receptors may provide effective treatment for ER-negative-AR-positive breast cancers.
Toth-Fejel
SuEllen
S
Division of Surgical Oncology, Department of General Surgery, Oregon Health & Science University, Portland 97201, USA. tothfeje@ohs.edu
Cheek
Julie
J
Calhoun
Kristine
K
Muller
Patrick
P
Pommier
Rodney F
RF
D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000473:pathology; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D011944:Receptors, Androgen / Q000032:analysis / Q000187:drug effects*; D011960:Receptors, Estrogen / Q000032:analysis / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D003687:Dehydroepiandrosterone