ArticleHuman molecular genetics2011
Steroid hormone modulation of RET through two estrogen responsive enhancers in breast cancer.
Article in Human molecular genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 44 citations in OpenAlex.
- Kinase Plasticity with Vandetanib Treatment Enhances Sensitivity to Tamoxifen in Estrogen Receptor Positive Breast Cancer.Molecular cancer therapeutics · 2026Article
- RET overexpression leads to increased brain metastatic competency in luminal breast cancer.Journal of the National Cancer Institute · 2024Article
- Super-enhancers: drivers of cells' identities and cells' debacles.Epigenomics · 2024Review
- Patient Sex and Origin Influence Distribution of Driver Genes and Clinical Presentation of Paraganglioma.Journal of the Endocrine Society · 2024Article
- Enhancer-activated RET confers protection against oxidative stress to KMT2A-rearranged acute myeloid leukemia.Cancer science · 2024Article
- REThinking the role of the RET oncogene in breast cancer.Frontiers in oncology · 2024Review
- Kinome Reprogramming Is a Targetable Vulnerability in ESR1 Fusion-Driven Breast Cancer.Cancer research · 2023Article
- Crucial role of the transcription factors family activator protein 2 in cancer: current clue and views.Journal of translational medicine · 2023Review
- RET signaling in breast cancer therapeutic resistance and metastasis.Breast cancer research : BCR · 2023Review
- Building integrative functional maps of gene regulation.Human molecular genetics · 2022Article
- Super-enhancer-controlled positive feedback loop BRD4/ERα-RET-ERα promotes ERα-positive breast cancer.Nucleic acids research · 2022Article
- RET signaling pathway and RET inhibitors in human cancer.Frontiers in oncology · 2022Review
- JMJD6 orchestrates a transcriptional program in favor of endocrine resistance in ER+ breast cancer cells.Frontiers in endocrinology · 2022Article
- Evidence for additive and synergistic action of mammalian enhancers during cell fate determination.eLife · 2021Article
- Highly interconnected enhancer communities control lineage-determining genes in human mesenchymal stem cells.Nature genetics · 2020Article
- DSCAM-AS1-Driven Proliferation of Breast Cancer Cells Involves Regulation of Alternative Exon Splicing and 3'-End Usage.Cancers · 2020Article
- Ret Receptor Has Distinct Alterations and Functions in Breast Cancer.Journal of mammary gland biology and neoplasia · 2020Review
- RET in breast cancer: pathogenic implications and mechanisms of drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- GDNF and the RET Receptor in Cancer: New Insights and Therapeutic Potential.Frontiers in physiology · 2018Review
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
RET, a gene causatively mutated in Hirschsprung disease and cancer, has recently been implicated in breast cancer estrogen (E2) independence and tamoxifen resistance. RET displays both E2 and retinoic acid (RA)-dependent transcriptional modulation in E2-responsive breast cancers. However, the regulatory elements through which the steroid hormone transcriptional regulation of RET is mediated are poorly defined. Recent genome-wide chromatin immunoprecipitation-based studies have identified 10 putative E2 receptor-alpha (ESR1) and RA receptor alpha-binding sites at the RET locus, of which we demonstrate only two (RET -49.8 and RET +32.8) display significant E2 regulatory response when assayed independently in MCF-7 breast cancer cells. We demonstrate that endogenous RET expression and RET -49.8 regulatory activity are cooperatively regulated by E2 and RA in breast cancer cells. We identify key sequences that are required for RET -49.8 and RET +32.8 E2 responsiveness, including motifs known to be bound by ESR1, FOXA1 and TFAP2C. We also report that both RET -49.8 regulatory activity and endogenous RET expression are completely dependent on ESR1 for their (E2)-induction and that ESR1 is sufficient to mediate the E2-induced enhancer activity of RET -49.8 and RET +32.8. Finally, using zebrafish transgenesis, we also demonstrate that RET -49.8 directs reporter expression in the central nervous system and peripheral nervous system consistent with the endogenous ret expression. Taken collectively, these data suggest that RET transcription in breast cancer cells is modulated by E2 via ESR1 acting on multiple elements collectively.
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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.