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

SuEllen Toth-Fejel, Julie Cheek, Kristine Calhoun, Patrick Muller, Rodney Pommier

    Research output: Contribution to journalArticle

    40 Citations (Scopus)

    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 2004

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    Androgen Receptors
    Estrogen Receptors
    Cell Proliferation
    Breast Neoplasms
    Dehydroepiandrosterone Sulfate
    Tamoxifen
    Therapeutics
    Mitogen-Activated Protein Kinases
    Growth
    Dehydroepiandrosterone
    Reverse Transcriptase Polymerase Chain Reaction
    Immunoassay
    Outcome Assessment (Health Care)

    ASJC Scopus subject areas

    • Surgery

    Cite this

    Estrogen and Androgen Receptors as Comediators of Breast Cancer Cell Proliferation : Providing a New Therapeutic Tool. / Toth-Fejel, SuEllen; Cheek, Julie; Calhoun, Kristine; Muller, Patrick; Pommier, Rodney.

    In: Archives of Surgery, Vol. 139, No. 1, 01.2004, p. 50-54.

    Research output: Contribution to journalArticle

    Toth-Fejel, SuEllen ; Cheek, Julie ; Calhoun, Kristine ; Muller, Patrick ; Pommier, Rodney. / Estrogen and Androgen Receptors as Comediators of Breast Cancer Cell Proliferation : Providing a New Therapeutic Tool. In: Archives of Surgery. 2004 ; Vol. 139, No. 1. pp. 50-54.
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    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.",
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