A new hormonal therapy for estrogen receptor-negative breast cancer

Chelsea Hardin, Rodney Pommier, Kristine Calhoun, Patrick Muller, Terisa Jackson, Su Ellen Johnson Pommier

    Research output: Contribution to journalArticle

    31 Citations (Scopus)

    Abstract

    Background: We postulate that the androgen dehydroepiandrosterone sulfate (DHEAS) may represent an innovative hormonal treatment for estrogen (ER), progesterone (PR) receptor-negative, but androgen receptor (AR)-positive breast cancers by inhibiting breast cancer cell growth through AR stimulation. Methods: Three ER,PR-negative breast cancer cell lines (HCC 1137, 1954, and 38), were treated with DHEAS. DHEAS-induced growth was measured by a methylthiotetrazole (MTT) proliferation assay and apoptosis by TUNEL fluorescence. Androgen receptor gene expression levels were determined using quantitative real-time polymerase chain reaction (q-RT-PCR). Results: HCC cell lines 1954 and 1937 were positive for AR expression; HCC 38 was weakly positive. MTT analysis showed DHEAS-induced decreases in cell proliferation of 47% in HCC 1937, 27% in HCC 1954, and 0.4% in HCC 38. Ten days of culturing HCC 1954 cells after the removal of DHEAS resulted in a 3.5-fold increase in growth. Continuous treatment for the same duration induced a 2.8-fold decrease in growth. Parallel experiments showed no significant changes in HCC 38 cultures. TUNEL assays showed DHEAS-induced apoptosis fold increases of 2.8 in HCC 1937, 1.9 in HCC 1954, and no significant difference in HCC 38 cultures. Q-RT-PCR of HCC 1954 cells showed a 6-fold DHEAS-induced decrease in AR gene expression at 4 h. Co-treatment with Casodex nullified this effect. Conclusions: DHEAS inhibited growth of ER,PR-negative, AR-positive breast cancer cells. DHEAS was cytotoxic to these breast cancer cells via the apoptosis pathway. DHEAS may be an effective treatment for a population previously excluded from hormone therapy.

    Original languageEnglish (US)
    Pages (from-to)1041-1046
    Number of pages6
    JournalWorld Journal of Surgery
    Volume31
    Issue number5
    DOIs
    StatePublished - May 2007

    Fingerprint

    Dehydroepiandrosterone Sulfate
    Estrogen Receptors
    Breast Neoplasms
    Androgen Receptors
    Therapeutics
    Growth
    In Situ Nick-End Labeling
    Apoptosis
    Progesterone
    Estrogens
    Gene Expression
    Cell Line
    Progesterone Receptors
    Androgens
    Real-Time Polymerase Chain Reaction
    Fluorescence
    Cell Proliferation
    Hormones
    Polymerase Chain Reaction

    ASJC Scopus subject areas

    • Surgery

    Cite this

    A new hormonal therapy for estrogen receptor-negative breast cancer. / Hardin, Chelsea; Pommier, Rodney; Calhoun, Kristine; Muller, Patrick; Jackson, Terisa; Pommier, Su Ellen Johnson.

    In: World Journal of Surgery, Vol. 31, No. 5, 05.2007, p. 1041-1046.

    Research output: Contribution to journalArticle

    Hardin, Chelsea ; Pommier, Rodney ; Calhoun, Kristine ; Muller, Patrick ; Jackson, Terisa ; Pommier, Su Ellen Johnson. / A new hormonal therapy for estrogen receptor-negative breast cancer. In: World Journal of Surgery. 2007 ; Vol. 31, No. 5. pp. 1041-1046.
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    abstract = "Background: We postulate that the androgen dehydroepiandrosterone sulfate (DHEAS) may represent an innovative hormonal treatment for estrogen (ER), progesterone (PR) receptor-negative, but androgen receptor (AR)-positive breast cancers by inhibiting breast cancer cell growth through AR stimulation. Methods: Three ER,PR-negative breast cancer cell lines (HCC 1137, 1954, and 38), were treated with DHEAS. DHEAS-induced growth was measured by a methylthiotetrazole (MTT) proliferation assay and apoptosis by TUNEL fluorescence. Androgen receptor gene expression levels were determined using quantitative real-time polymerase chain reaction (q-RT-PCR). Results: HCC cell lines 1954 and 1937 were positive for AR expression; HCC 38 was weakly positive. MTT analysis showed DHEAS-induced decreases in cell proliferation of 47{\%} in HCC 1937, 27{\%} in HCC 1954, and 0.4{\%} in HCC 38. Ten days of culturing HCC 1954 cells after the removal of DHEAS resulted in a 3.5-fold increase in growth. Continuous treatment for the same duration induced a 2.8-fold decrease in growth. Parallel experiments showed no significant changes in HCC 38 cultures. TUNEL assays showed DHEAS-induced apoptosis fold increases of 2.8 in HCC 1937, 1.9 in HCC 1954, and no significant difference in HCC 38 cultures. Q-RT-PCR of HCC 1954 cells showed a 6-fold DHEAS-induced decrease in AR gene expression at 4 h. Co-treatment with Casodex nullified this effect. Conclusions: DHEAS inhibited growth of ER,PR-negative, AR-positive breast cancer cells. DHEAS was cytotoxic to these breast cancer cells via the apoptosis pathway. DHEAS may be an effective treatment for a population previously excluded from hormone therapy.",
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