ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
Opposing effects of Runx2 and estradiol on breast cancer cell proliferation: in vitro identification of reciprocally regulated gene signature related to clinical letrozole responsiveness.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 43 citations in OpenAlex.
- Runx1 and Runx2 act in concert to suppress Wnt/β-catenin-driven mammary tumourigenesis.British journal of cancer · 2026Article
- Review
- Comprehensive Analysis of RUNX and TGF-β Mediated Regulation of Immune Cell Infiltration in Breast Cancer.Frontiers in cell and developmental biology · 2021Article
- RUNX2 as a promising therapeutic target for malignant tumors.Cancer management and research · 2021Review
- Personalized Web-Based Cognitive Rehabilitation Treatments for Patients with Traumatic Brain Injury: Cluster Analysis.JMIR medical informatics · 2020Article
- SET7/9 promotes multiple malignant processes in breast cancer development via RUNX2 activation and is negatively regulated by TRIM21.Cell death & disease · 2020Article
- Identification of the hub genes RUNX2 and FN1 in gastric cancer.Open medicine (Warsaw, Poland) · 2020Article
- Runx2 is required for activity of CD44American journal of translational research · 2020Article
- Higher order genomic organization and epigenetic control maintain cellular identity and prevent breast cancer.Genes, chromosomes & cancer · 2019Review
- LINC01638 silencing inhibits cancer cell proliferation in colorectal adenocarcinoma through interaction with RUNX2.Molecular medicine reports · 2019Article
- Estrogens and selective estrogen receptor modulators differentially antagonize Runx2 in ST2 mesenchymal progenitor cells.The Journal of steroid biochemistry and molecular biology · 2018Article
- Antitumor efficacy of the Runx2-dendritic cell vaccine in triple-negative breast cancerOncology letters · 2018Article
- Relationship between RUNX1 and AXIN1 in ER-negative versus ER-positive Breast Cancer.Cell cycle (Georgetown, Tex.) · 2017Article
- Roles of RUNX in Hippo Pathway Signaling.Advances in experimental medicine and biology · 2017Review
- Glucocorticoids Hijack Runx2 to Stimulate Wif1 for Suppression of Osteoblast Growth and Differentiation.Journal of cellular physiology · 2017Article
- Runx2 Expression as a Potential Prognostic Marker in Invasive Ductal Breast Carcinoma.Pathology oncology research : POR · 2016Article
- Transcription factor RUNX2 up-regulates chemokine receptor CXCR4 to promote invasive and metastatic potentials of human gastric cancer.Oncotarget · 2016Article
- RUNX1 prevents oestrogen-mediated AXIN1 suppression and β-catenin activation in ER-positive breast cancer.Nature communications · 2016Article
- The RUNX2 Transcription Factor Negatively Regulates SIRT6 Expression to Alter Glucose Metabolism in Breast Cancer Cells.Journal of cellular biochemistry · 2015Article
- Runx1 is associated with breast cancer progression in MMTV-PyMT transgenic mice and its depletion in vitro inhibits migration and invasion.Journal of cellular physiology · 2015Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
purposeTo assess the clinical significance of the interaction between estrogen and Runx2 signaling, previously shown in vitro. EXPERIMENTAL
designMCF7/Rx2(dox) breast cancer cells were treated with estradiol and/or doxycycline to induce Runx2, and global gene expression was profiled to define genes regulated by estradiol, Runx2, or both. Anchorage-independent growth was assessed by soft-agar colony formation assays. Expression of gene sets defined using the MCF7/Rx2(dox) system was analyzed in pre- and on-treatment biopsies from hormone receptor-positive patients undergoing neoadjuvant letrozole treatment in two independent studies, and short-term changes in gene expression were correlated with tumor size reduction or Ki67 index at surgery.
resultsReflecting its oncogenic property, estradiol strongly promoted soft-agar colony formation, whereas Runx2 blocked this process suggesting tumor suppressor property. Transcriptome analysis of MCF7/Rx2(dox) cells treated with estradiol and/or doxycycline showed reciprocal attenuation of Runx2 and estrogen signaling. Correspondingly in breast cancer tumors, expression of estradiol- and Runx2-regulated genes was inversely correlated, and letrozole increased expression of Runx2-stimulated genes, as defined in the MCF7/Rx2(dox) model. Of particular interest was a gene set upregulated by estradiol and downregulated by Runx2 in vitro; its short-term response to letrozole treatment associated with tumor size reduction and Ki67 index at surgery better than other estradiol-regulated gene sets.
conclusionThis work provides clinical evidence for the importance of antagonism between Runx2 and E2 signaling in breast cancer. Likely sensing the tension between them, letrozole responsiveness of a genomic node, positively regulated by estradiol and negatively regulated by Runx2 in vitro, best correlated with the clinical efficacy of letrozole treatment.
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