ArticleHormone molecular biology and clinical investigation2011
The Conformation of the Estrogen Receptor Directs Estrogen-Induced Apoptosis in Breast Cancer: A Hypothesis.
Article in Hormone molecular biology and clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- Estrogen Receptor Complex to Trigger or Delay Estrogen-Induced Apoptosis in Long-Term Estrogen Deprived Breast Cancer.Frontiers in endocrinology · 2022Review
- Turning scientific serendipity into discoveries in breast cancer research and treatment: a tale of PhD students and a 50-year roaming tamoxifen team.Breast cancer research and treatment · 2021Review
- The Structure-Function Relationship of Angular Estrogens and Estrogen Receptor Alpha to Initiate Estrogen-Induced Apoptosis in Breast Cancer Cells.Molecular pharmacology · 2020Article
- Endoxifen, 4-Hydroxytamoxifen and an Estrogenic Derivative Modulate Estrogen Receptor Complex Mediated Apoptosis in Breast Cancer.Molecular pharmacology · 2018Article
- Supraphysiologic Testosterone Therapy in the Treatment of Prostate Cancer: Models, Mechanisms and Questions.Cancers · 2017Review
- The molecular, cellular and clinical consequences of targeting the estrogen receptor following estrogen deprivation therapy.Molecular and cellular endocrinology · 2015Review
- Pharmacological relevance of endoxifen in a laboratory simulation of breast cancer in postmenopausal patients.Journal of the National Cancer Institute · 2014Article
- Differences in the rate of oestrogen-induced apoptosis in breast cancer by oestradiol and the triphenylethylene bisphenol.British journal of pharmacology · 2014Article
- Defining the conformation of the estrogen receptor complex that controls estrogen-induced apoptosis in breast cancer.Molecular pharmacology · 2014Article
- Delayed triggering of oestrogen induced apoptosis that contrasts with rapid paclitaxel-induced breast cancer cell death.British journal of cancer · 2014Article
- Molecular mechanism of action of bisphenol and bisphenol A mediated by oestrogen receptor alpha in growth and apoptosis of breast cancer cells.British journal of pharmacology · 2013Article
- Scientific rationale for postmenopause delay in the use of conjugated equine estrogens among postmenopausal women that causes reduction in breast cancer incidence and mortality.Menopause (New York, N.Y.) · 2013Article
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundEstrogens are classified as type I (planar) and type II (angular) based on their structures. In this study we have used triphenylethylenes (TPEs) compounds related to 4OHT to address the hypothesis that the conformation of the liganded estrogen receptor (ERα) may dictate the E2-induced apoptosis of the ER+ breast cancer cells. MATERIALS AND
methodsERα positive MCF7:5C cells were used to study the apoptosis induced by E2, 4OHT and TPEs. Growth and apoptosis assay were used to evaluate apoptosis and the ability to reverse the E2-induced apoptosis. ERα protein were measured by western blotting to investigate the destruction of ERα by TPEs in MCF7 cells. ChIP assay were performed to study the in-vivo recruitment of ERα and SRC3 at classical E2-responsive promoter TFF1 (PS2) by TPEs. Molecular modeling was used to predict the binding mode of the TPE to the ERα.
resultsTPEs were not only unable to induce efficient apoptosis in MCF7:5C cells but also reversed the E2-induced apoptosis similar to 4OHT. Furthermore, the TPEs and 4OHT did not reduce the ERα protein levels unlike E2. ChIP assay confirmed very weak recruitment of SRC3 despite modest recruitment of ERα in the presence of TPEs. Molecular modeling suggested the TPE would bind in antagonistic mode with the ERα.
conclusionOur results advances the hypothesis that the TPE liganded ERα complex structurally resembles the 4OHT bound ERα and cannot efficiently recruit co-activator SRC3. As a result, the TPE complex cannot induce apoptosis of ER+ breast cancer cells although it may cause growth of the breast cancer cells. The conformation of the estrogen-ER complex differentially controls growth and apoptosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.