Estrogen and Androgen Receptors as Comediators of Breast Cancer Cell Proliferation: Providing a New Therapeutic Tool

Su Ellen Toth-Fejel, Julie Cheek, Kristine Calhoun, Patrick Muller, Rodney F. Pommier

    Research output: Contribution to journalArticle

    41 Scopus citations

    Abstract

    Hypothesiss. 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.

    Original languageEnglish (US)
    Pages (from-to)50-54
    Number of pages5
    JournalArchives of Surgery
    Volume139
    Issue number1
    DOIs
    StatePublished - Jan 1 2004

    ASJC Scopus subject areas

    • Surgery

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