Estrogen and androgen receptors as comediators of breast cancer cell proliferation: providing a new therapeutic tool.

Hypothesis: Dehydroepiandrosterone sulfate (DHEA-S) comediates breast cancer progression via estrogen receptors (ERs) and androgen receptors (ARs).

Design: 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.

Setting: University Surgical Oncology Research Laboratory.

Main Outcome Measures: 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.