ArticleMolecular cancer research : MCR2016
SIX1 Oncoprotein as a Biomarker in a Model of Hormonal Carcinogenesis and in Human Endometrial Cancer.
Article in Molecular cancer research : MCR, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 60 citations in OpenAlex.
- Article
- Effect of Diethylstilbestrol on Implantation and Decidualization in Mice.International journal of molecular sciences · 2025Article
- Article
- Article
- Targeting sine oculis homeoprotein 1 (SIX1): A review of oncogenic roles and potential natural product therapeutics.Heliyon · 2024Review
- Combination of computational new approach methodologies for enhancing evidence of biological pathway conservation across species.The Science of the total environment · 2024Article
- Multiple tissue-specific epigenetic alterations regulate persistent gene expression changes following developmental DES exposure in mouse reproductive tissues.Epigenetics · 2023Article
- Developmental estrogen exposure in mice disrupts uterine epithelial cell differentiation and causes adenocarcinoma via Wnt/β-catenin and PI3K/AKT signaling.PLoS biology · 2023Article
- An EMT-related genes signature as a prognostic biomarker for patients with endometrial cancer.BMC cancer · 2023Article
- Development of adverse outcome pathways relevant for the identification of substances having endocrine disruption properties Uterine adenocarcinoma as adverse outcome.EFSA journal. European Food Safety Authority · 2023Article
- Upregulation of the oestrogen target gene SIX1 is associated with higher growth speed and decreased survival in HCV-positive women with hepatocellular carcinoma.Oncology letters · 2022Article
- Article
- Developmental exposure to phytoestrogens found in soy: New findings and clinical implications.Biochemical pharmacology · 2022Review
- KIFC1 promotes aerobic glycolysis in endometrial cancer cells by regulating the c-myc pathway.Journal of bioenergetics and biomembranes · 2021Article
- MicroRNA-155-3p promotes glioma progression and temozolomide resistance by targeting Six1.Journal of cellular and molecular medicine · 2020Article
- Uterine Patterning, Endometrial Gland Development, and Implantation Failure in Mice Exposed Neonatally to Genistein.Environmental health perspectives · 2020Article
- Alternatively Constructed Estrogen Receptor Alpha-Driven Super-Enhancers Result in Similar Gene Expression in Breast and Endometrial Cell Lines.International journal of molecular sciences · 2020Article
- Identification of EMT-Related Gene Signatures to Predict the Prognosis of Patients With Endometrial Cancer.Frontiers in genetics · 2020Article
- SIX1 Regulates Aberrant Endometrial Epithelial Cell Differentiation and Cancer Latency Following Developmental Estrogenic Chemical Exposure.Molecular cancer research : MCR · 2019Article
- Endocrine Disruption and Reproductive Pathology.Toxicologic pathology · 2019Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
unlabelledThe oncofetal protein sine oculis-related homeobox 1 (SIX1) is a developmental transcription factor associated with carcinogenesis in several human cancer types but has not been investigated in human endometrial cancer. In a model of hormonal carcinogenesis, mice neonatally exposed to the soy phytoestrogen genistein (GEN) or the synthetic estrogen diethylstilbestrol (DES) develop endometrial cancer as adults. Previously, we demonstrated that SIX1 becomes aberrantly expressed in the uteri of these mice. Here, we used this mouse model to investigate the role of SIX1 expression in endometrial carcinoma development and used human tissue microarrays to explore the utility of SIX1 as a biomarker in human endometrial cancer. In mice neonatally exposed to GEN or DES, the Six1 transcript level increased dramatically over time in uteri at 6, 12, and 18 months of age and was associated with development of endometrial carcinoma. SIX1 protein localized within abnormal basal cells and all atypical hyperplastic and neoplastic lesions. These findings indicate that developmental estrogenic chemical exposure induces persistent endometrial SIX1 expression that is strongly associated with abnormal cell differentiation and cancer development. In human endometrial tissue specimens, SIX1 was not present in normal endometrium but was expressed in a subset of endometrial cancers in patients who were also more likely to have late-stage disease. These findings identify SIX1 as a disease biomarker in a model of hormonal carcinogenesis and suggest that SIX1 plays a role in endometrial cancer development in both mice and women. IMPLICATIONS: The SIX1 oncoprotein is aberrantly expressed in the endometrium following developmental exposure to estrogenic chemicals, correlates with uterine cancer, and is a biomarker in human endometrial cancers. Mol Cancer Res; 14(9); 849-58. ©2016 AACR.
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