ArticleMolecular endocrinology (Baltimore, Md.)2009
Resistance to antiestrogen arzoxifene is mediated by overexpression of cyclin D1.
Article in Molecular endocrinology (Baltimore, Md.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- FOXA1 levels are decreased in pleural breast cancer metastases after adjuvant endocrine therapy, and this is associated with poor outcome.Molecular oncology · 2018Trial
- Effects of cyclin D1 gene amplification and protein expression on time to recurrence in postmenopausal breast cancer patients treated with anastrozole or tamoxifen: a TransATAC study.Breast cancer research : BCR · 2012Trial
- Endometrial tumorigenesis involves epigenetic plasticity demarcating non-coding somatic mutations and 3D-genome alterations.Genome biology · 2025Article
- A CRISPR-Cas9 screen identifies essential CTCF anchor sites for estrogen receptor-driven breast cancer cell proliferation.Nucleic acids research · 2019Article
- Mitotic count can predict tamoxifen benefit in postmenopausal breast cancer patients while Ki67 score cannot.BMC cancer · 2018Article
- Induction of HEXIM1 activities by HMBA derivative 4a1: Functional consequences and mechanism.Cancer letters · 2016Article
- Protein Kinase A-induced tamoxifen resistance is mediated by anchoring protein AKAP13.BMC cancer · 2015Article
- Nuclear receptors and their selective pharmacologic modulators.Pharmacological reviews · 2013Review
- Ceramide-orchestrated signalling in cancer cells.Nature reviews. Cancer · 2013Review
- Association of Over-Expressed Estrogen Receptor Alpha with Development of Tamoxifen Resistant Hyperplasia and Adenocarcinomas in Genetically Engineered Mice.Anatomy & physiology : current research · 2012Article
- The two faces of FBW7 in cancer drug resistance.BioEssays : news and reviews in molecular, cellular and developmental biology · 2011Review
- Article
- SLUG-induced elevation of D1 cyclin in breast cancer cells through the inhibition of its ubiquitination.The Journal of biological chemistry · 2011Article
- A role for estrogen receptor phosphorylation in the resistance to tamoxifen.International journal of breast cancer · 2011Article
- Ron receptor tyrosine kinase activation confers resistance to tamoxifen in breast cancer cell lines.Neoplasia (New York, N.Y.) · 2010Article
- Estrogen receptor alpha 46 is reduced in tamoxifen resistant breast cancer cells and re-expression inhibits cell proliferation and estrogen receptor alpha 66-regulated target gene transcription.Molecular and cellular endocrinology · 2010Article
- FOXM1 is a transcriptional target of ERalpha and has a critical role in breast cancer endocrine sensitivity and resistance.Oncogene · 2010Article
- Oestrogen receptor beta is involved in the actions of oestrogens in the brain for affective behaviour, but not trophic effects in peripheral tissues.Journal of neuroendocrinology · 2010Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Resistance to tamoxifen treatment occurs in approximately 50% of the estrogen receptor (ER)alpha-positive breast cancer patients. Resistant patients would benefit from treatment with other available antiestrogens. Arzoxifene is an effective growth inhibitor of ERalpha-positive breast cancer cells, including tamoxifen-resistant tumors. In this study, we show that overexpression of a regular component of the ERalpha transcription factor complex, cyclin D1, which occurs in approximately 40% of breast cancer patients, renders cells resistant to the new promising antiestrogen, arzoxifene. Overexpression of cyclin D1 alters the conformation of ERalpha in the presence of arzoxifene. In this altered conformation, ERalpha still recruits RNA polymerase II to an estrogen response element-containing promoter, inducing transcription of an ERalpha-dependent reporter gene and of endogenous pS2, and promoting arzoxifene-stimulated growth of MCF-7 cells. Arzoxifene is then converted from an ERalpha antagonist into an agonist. This can be explained by a stabilization of the ERalpha/steroid receptor coactivator-1 complex in the presence of arzoxifene, only when cyclin D1 is overexpressed. These results indicate that subtle changes in the conformation of ERalpha upon binding to antiestrogen are at the basis of resistance to antiestrogens.
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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.