ArticlePloS one2014
DNA methylation of heparanase promoter influences its expression and associated with the progression of human breast cancer.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- The Pathophysiological Functions of Heparanases: From Evolution, Structural and Tissue-Specific Perspectives.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Investigating the Role of Heparanase in Breast Cancer Development Utilising the MMTV-PyMT Murine Model of Mammary Carcinoma.Cancers · 2023Article
- The Heparanase Regulatory Network in Health and Disease.International journal of molecular sciences · 2021Review
- Article
- Heparanase: a potential marker of worse prognosis in estrogen receptor-positive breast cancer.NPJ breast cancer · 2021Article
- Reactivation of oncogenes involved in G1/S transcription and apoptosis pathways by low dose decitabine promotes HT29 human colon cancer cell growth in vitro.American journal of translational research · 2020Article
- Gene expression changes and promoter methylation with the combined effects of estradiol and leptin in uterine tissue of the ovariectomized mice model of menopause.Molecular biology reports · 2020Article
- Host Enzymes Heparanase and Cathepsin L Promote Herpes Simplex Virus 2 Release from Cells.Journal of virology · 2018Article
- Sulfotransferase and Heparanase: Remodeling Engines in Promoting Virus Infection and Disease Development.Frontiers in pharmacology · 2018Review
- Functional and prognostic significance of long non-coding RNA MALAT1 as a metastasis driver in ER negative lymph node negative breast cancer.Oncotarget · 2016Article
- A study of the role of Notch1 and JAG1 gene methylation in development of breast cancer.Medical oncology (Northwood, London, England) · 2016Article
- Continued use of MDA-MB-435, a melanoma cell line, as a model for human breast cancer, even in year, 2014.NPJ breast cancer · 2015Article
- The close correlation between heparanase and COX-2 expression in lymphangiogenesis of cervical cancer.Medical oncology (Northwood, London, England) · 2014Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heparanase promotes tumor invasion and metastasis in several malignancies including breast cancer. However, the roles and regulation mechanisms of heparanase during breast cancer progression are still not fully understood. The aim of this study is to determine the differential regulation of heparanase gene expression in specific stages of breast cancer by DNA methylation. We detected levels of heparanase expression and DNA methylation patterns of its promoter in breast cancer cell lines (MCF-7 and MDA-MB-435) and clinical tissues, respectively. It has been observed that heparanase is highly expressed in the invasive MDA-MB-435 cells with low methylation modification in the heparanase promoter. In contrast, lower expression of heparanase in MCF-7 cells is accompanied by higher methylation in the promoter. Treatment of MCF-7 cells with 5-aza-2'-deoxycytidine (5-aza-dC), a potent demethylating agent, results in induction of heparanase expression and higher invasion potential in vitro and leads to an advantage of tumor formation in vivo. In 54 tissue samples, cancer samples at late stages (stage IV) showed the highest heparanase expression accomplished by little DNA methylation. On the contrary, methylation prevalence is highest in normal tissue and inversely correlated with heparanase expression. A significant correlation between DNA methylation and clinical stage was demonstrated (p = 0.012). Collectively, these results demonstrate that DNA methylation play the regulation role in heparanase gene in different stages of breast cancer and present a direct effect on tumor progression.
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