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Androgen receptor overexpression induces tamoxifen resistance in human breast cancer cells | Breast Cancer Research and Treatment
Description:
Although the androgen receptor (AR) is a known clinical target in prostate cancer, little is known about its possible role in breast cancer. We have investigated the role of AR expression in human breast cancer in response to treatment with the antiestrogen tamoxifen. Resistance to tamoxifen is a major problem in treating women with breast cancer. By gene expression profiling, we found elevated AR and reduced estrogen receptor (ER) α mRNA in tamoxifen-resistant tumors. Exogenous overexpression of AR rendered ERα-positive MCF-7 breast cancer cells resistant to the growth-inhibitory effects of tamoxifen in anchorage-independent growth assays and in xenograft studies in athymic nude mice. AR-overexpressing cells remained sensitive to growth stimulation with dihydrotestosterone. Treatment with the AR antagonist Casodex™ (bicalutamide) reversed this resistance, demonstrating the involvement of AR signaling in tamoxifen resistance. In AR-overexpressing cells, tamoxifen induced transcriptional activation by ERα that could be blocked by Casodex, suggesting that AR overexpression enhances tamoxifen’s agonistic properties. Our data suggest a role for AR overexpression as a novel mechanism of hormone resistance, so that AR may offer a new clinical therapeutic target in human breast cancers.
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Keywords {🔍}
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Topics {✒️}
er/her2-positive breast cancer month download article/chapter her2/neu kinase-dependent modulation growth factor cross-talk node-positive breast cancer tamoxifen-resistant mcf-7 cells oestrogen receptor-mediated modulation antagonist-occupied steroid receptors tamoxifen-resistant tumorigenic growth human estrogen receptor-alpha nih grants p01-ca30195 anchorage-independent growth assays clinical therapeutic target estrogen receptor-positive breast cancer cells ar-overexpressing cells full article pdf hormone resistance related subjects progesterone receptor action human androgen receptor negative predictive factor human breast cancer androgen receptor expression oestrogen receptor-alpha mcf-7 cells transfected tamoxifen-resistant tumors anti-hormonal therapy adjuvant hormonal therapy combination hormonal therapy breast cancer patients human breast cancers progesterone receptor status estrogen receptor alpha prostate cancer cells steroid antagonist action metastatic breast cancer recurrent breast cancer advanced breast cancer breast cancer contribute privacy choices/manage cookies androgen receptor coactivator reduced estrogen receptor metastatic estrogen receptor postmenopausal breast cancer clinical breast cancer fluoxymesterone versus tamoxifen single living cells androgens modulate expression growth factor ii
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headline:Androgen receptor overexpression induces tamoxifen resistance in human breast cancer cells
description:Although the androgen receptor (AR) is a known clinical target in prostate cancer, little is known about its possible role in breast cancer. We have investigated the role of AR expression in human breast cancer in response to treatment with the antiestrogen tamoxifen. Resistance to tamoxifen is a major problem in treating women with breast cancer. By gene expression profiling, we found elevated AR and reduced estrogen receptor (ER) α mRNA in tamoxifen-resistant tumors. Exogenous overexpression of AR rendered ERα-positive MCF-7 breast cancer cells resistant to the growth-inhibitory effects of tamoxifen in anchorage-independent growth assays and in xenograft studies in athymic nude mice. AR-overexpressing cells remained sensitive to growth stimulation with dihydrotestosterone. Treatment with the AR antagonist Casodex™ (bicalutamide) reversed this resistance, demonstrating the involvement of AR signaling in tamoxifen resistance. In AR-overexpressing cells, tamoxifen induced transcriptional activation by ERα that could be blocked by Casodex, suggesting that AR overexpression enhances tamoxifen’s agonistic properties. Our data suggest a role for AR overexpression as a novel mechanism of hormone resistance, so that AR may offer a new clinical therapeutic target in human breast cancers.
datePublished:2009-06-17T00:00:00Z
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Androgen receptor
Breast cancer
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Oncology
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headline:Androgen receptor overexpression induces tamoxifen resistance in human breast cancer cells
description:Although the androgen receptor (AR) is a known clinical target in prostate cancer, little is known about its possible role in breast cancer. We have investigated the role of AR expression in human breast cancer in response to treatment with the antiestrogen tamoxifen. Resistance to tamoxifen is a major problem in treating women with breast cancer. By gene expression profiling, we found elevated AR and reduced estrogen receptor (ER) α mRNA in tamoxifen-resistant tumors. Exogenous overexpression of AR rendered ERα-positive MCF-7 breast cancer cells resistant to the growth-inhibitory effects of tamoxifen in anchorage-independent growth assays and in xenograft studies in athymic nude mice. AR-overexpressing cells remained sensitive to growth stimulation with dihydrotestosterone. Treatment with the AR antagonist Casodex™ (bicalutamide) reversed this resistance, demonstrating the involvement of AR signaling in tamoxifen resistance. In AR-overexpressing cells, tamoxifen induced transcriptional activation by ERα that could be blocked by Casodex, suggesting that AR overexpression enhances tamoxifen’s agonistic properties. Our data suggest a role for AR overexpression as a novel mechanism of hormone resistance, so that AR may offer a new clinical therapeutic target in human breast cancers.
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Breast cancer
Tamoxifen resistance
Oncology
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