ArticleBreast cancer research : BCR2009
Hes-6, an inhibitor of Hes-1, is regulated by 17beta-estradiol and promotes breast cancer cell proliferation.
Article in Breast cancer research : BCR, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 33 citations in OpenAlex.
- HES1 oscillations are required for cell cycle reentry in oestrogen receptor-positive breast cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Pan-cancer analysis reveals dual roles of HES6 in cancer immunity and prognosis.Discover oncology · 2025Article
- Article
- Recent advances in understanding the role of HES6 in cancers.Theranostics · 2022Review
- Notch Signalling in Breast Development and Cancer.Frontiers in cell and developmental biology · 2021Review
- A Small-Molecule Tankyrase Inhibitor Reduces Glioma Stem Cell Proliferation and Sphere Formation.Cancers · 2020Article
- Prognostic genes of triple-negative breast cancer identified by weighted gene co-expression network analysis.Oncology letters · 2020Article
- Overexpression of HES6 has prognostic value and promotes metastasis via the Wnt/β-catenin signaling pathway in colorectal cancer.Oncology reports · 2018Article
- Drosophila Protein Kinase CK2: Genetics, Regulatory Complexity and Emerging Roles during Development.Pharmaceuticals (Basel, Switzerland) · 2016Review
- The complex nature of oestrogen signalling in breast cancer: enemy or ally?Bioscience reports · 2016Review
- Hairy and Enhancer of Split 6 (Hes6) Deficiency in Mouse Impairs Neuroblast Differentiation in Dentate Gyrus Without Affecting Cell Proliferation and Integration into Mature Neurons.Cellular and molecular neurobiology · 2016Article
- HES6 drives a critical AR transcriptional programme to induce castration-resistant prostate cancer through activation of an E2F1-mediated cell cycle network.EMBO molecular medicine · 2014Article
- Early aberrant DNA methylation events in a mouse model of acute myeloid leukemia.Genome medicine · 2014Article
- Regulation of angiogenesis via Notch signaling in breast cancer and cancer stem cells.Biochimica et biophysica acta · 2013Review
- Genome-wide microarrray analysis reveals roles for the REF-1 family member HLH-29 in ferritin synthesis and peroxide stress response.PloS one · 2013Article
- Human achaete-scute homolog-1 expression in neuroendocrine breast carcinoma.Virchows Archiv : an international journal of pathology · 2012Article
- HLH-29 regulates ovulation in C. elegans by targeting genes in the inositol triphosphate signaling pathway.Biology open · 2012Article
- HES6 gene is selectively overexpressed in glioma and represents an important transcriptional regulator of glioma proliferation.Oncogene · 2012Article
- Notch signaling as a therapeutic target for breast cancer treatment?Breast cancer research : BCR · 2011Review
- Role of Notch and its oncogenic signaling crosstalk in breast cancer.Biochimica et biophysica acta · 2011Review
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionHes-6 is a member of the basic helix-loop-helix (bHLH) family of transcription factors, and its overexpression has been reported in metastatic cancers of different origins. Hes-6 has been described as an inhibitor of Hes-1 during neuronal development, although its function in cancer is not known. In this study, we investigated the function of Hes-6 in breast cancer and tested the hypothesis that Hes-6 enhances breast cancer cell proliferation and is regulated by estrogen.
methodsTo investigate the function of Hes-6, T47D cells stably expressing Hes-6 were generated by lentiviral transduction, and conversely, siRNA also was used to knock down Hes-6 expression in breast cancer cells. The Hes-6-expressing T47D cells were transplanted into immunodeficient mice to study effects on tumor growth.
resultsWe found that Hes-6 expression was significantly higher in the high-grade, estrogen receptor (ER)alpha-negative SKBR3 and MDA-MB-231 cells compared with the ERalpha-positive, non-metastasizing T47D and MCF-7 breast carcinoma cells. Moreover, the level of Hes-6 mRNA was 28 times higher in breast cancer samples compared with normal breast samples. In Hes-6-expressing T47D cells, Hes-6 ectopic expression was shown to stimulate cell proliferation in vitro as well as breast tumor growth in xenografts. Moreover, expression of Hes-6 resulted in induction of E2F-1, a crucial target gene for the transcriptional repressor Hes-1. Consistently, silencing of Hes-6 by siRNA resulted in downregulation of E2F-1 expression, whereas estrogen treatment caused induction of Hes-6 and downstream targets hASH-1 and E2F-1 in MCF-7 cells.
conclusionsTogether, the data suggest that Hes-6 is a potential oncogene overexpressed in breast cancer, with a tumor-promoting and proliferative function. Furthermore, Hes-6 is a novel estrogen-regulated gene in breast cancer cells. An understanding of the role and regulation of Hes-6 could provide insights into estrogen signaling and endocrine resistance in breast cancer and, hence, could be important for the development of novel anticancer drugs.
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