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Providing a New Therapeutic Tool

SuEllen Toth-Fejel, PhD; Julie Cheek, MD; Kristine Calhoun, MD; Patrick Muller, BS; Rodney F. Pommier, MD

Arch Surg. 2004;139:50-54.

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 228µM 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.

From the Division of Surgical Oncology, Department of General Surgery, Oregon Health & Science University, Portland (Drs Toth-Fejel, Calhoun, and Pommier and Mr Muller); and Department of Surgery, Akron General Medical Center, Akron, Ohio (Dr Cheek).

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