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A new hormonal therapy for estrogen receptor-negative breast cancer
Chelsea Hardin1, Rodney Pommier, Kristine Calhoun
1Division of Surgical Oncology, Department of General Surgery, Oregon Health & Science University, Portland, Oregon 97201, USA.
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.
Insights
Dehydroepiandrosterone sulfate (DHEAS) shows promise in treating specific breast cancers. This androgen hormone inhibited growth and induced apoptosis in estrogen/progesterone receptor-negative, androgen receptor-positive breast cancer cells.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Estrogen receptor (ER) and progesterone receptor (PR) negative breast cancers often lack effective hormonal therapies.
- Androgen receptor (AR)-positive breast cancers represent a subset that may respond to different hormonal interventions.
Purpose of the Study:
- To investigate the potential of dehydroepiandrosterone sulfate (DHEAS) as a novel hormonal treatment for ER, PR-negative, AR-positive breast cancers.
- To assess the effects of DHEAS on breast cancer cell growth, proliferation, and apoptosis.
Main Methods:
- Three ER, PR-negative breast cancer cell lines (HCC 1137, 1954, 38) were treated with DHEAS.
- Cell proliferation was measured using MTT assays.
- Apoptosis was assessed via TUNEL fluorescence.
- Androgen receptor gene expression was quantified using qRT-PCR.
Main Results:
- DHEAS significantly decreased cell proliferation in AR-positive cell lines HCC 1937 (47%) and HCC 1954 (27%).
- DHEAS induced apoptosis in HCC 1937 (2.8-fold increase) and HCC 1954 (1.9-fold increase).
- DHEAS treatment led to a 6-fold decrease in AR gene expression in HCC 1954 cells within 4 hours, an effect nullified by co-treatment with Casodex.
Conclusions:
- Dehydroepiandrosterone sulfate (DHEAS) demonstrates inhibitory effects on the growth of ER, PR-negative, AR-positive breast cancer cells.
- DHEAS exhibits cytotoxicity through the induction of apoptosis in these specific cancer cells.
- DHEAS presents a potential therapeutic option for breast cancer patients previously ineligible for traditional hormone therapy.
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