ArticleCarcinogenesis2009
BTG3 tumor suppressor gene promoter demethylation, histone modification and cell cycle arrest by genistein in renal cancer.
Article in Carcinogenesis, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
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Who cites it
104 citing papers in PubMed, 211 citations in OpenAlex.
- Role of chromatin remodeling and immunopharmacology in cancer therapy.Molecular medicine (Cambridge, Mass.) · 2026Review
- The nutrigenomic-epigenetic axis in cancer: from dietary bioactives to precision oncology.Nutrition & metabolism · 2026Review
- The potential and promise of natural antioxidants as epigenetic modulators in oral squamous cell carcinoma.Cancer chemotherapy and pharmacology · 2026Review
- The ESRP1 promoter reporter can function as an in vivo sensor of DNA methyltransferase inhibition.BMC biotechnology · 2025Article
- BTG3-dependent VCP/p97 nuclear translocation is required for efficient repair of UV-induced DNA lesions.Nucleic acids research · 2025Article
- Natural Compounds in Cancer Therapy: Revealing the Role of Flavonoids in Renal Cell Carcinoma Treatment.Biomolecules · 2025Review
- Role of DNA methylation transferase in urinary system diseases: From basic to clinical perspectives (Review).International journal of molecular medicine · 2025Review
- A keratinocyte-adipocyte signaling loop is reprogrammed by loss of BTG3 to augment skin carcinogenesis.Cell death and differentiation · 2024Article
- Inhibition of Cancer Development by Natural Plant Polyphenols: Molecular Mechanisms.International journal of molecular sciences · 2023Review
- In utero and postnatal exposure to Foeniculum vulgare and Linum usitatissimum seed extracts: modifications of key enzymes involved in epigenetic regulation and estrogen receptors expression in the offspring's ovaries of NMRI mice.BMC complementary medicine and therapies · 2023Article
- Effects of Genistein on Common Kidney Diseases.Nutrients · 2022Review
- Methyl Group Metabolism in Differentiation, Aging, and Cancer.International journal of molecular sciences · 2022Review
- Review
- Article
- The clinicopathological significances and related signal pathways of BTG3 mRNA expression in cancers: A bioinformatics analysis.Frontiers in genetics · 2022Article
- Genistein-induced Anticancer Effects on Acute Leukemia Cells Involve the Regulation of Wnt Signaling Pathway Through H4K20me1 Rather Than DNA Demethylation.Current medical science · 2021Article
- Review
- Genistein: An Integrative Overview of Its Mode of Action, Pharmacological Properties, and Health Benefits.Oxidative medicine and cellular longevity · 2021Review
- Loss of the tumor suppressor BTG3 drives a pro-angiogenic tumor microenvironment through HIF-1 activation.Cell death & disease · 2020Article
- The Impact of Natural Dietary Compounds and Food-Borne Mycotoxins on DNA Methylation and Cancer.Cells · 2020Review
44 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
BTG3/ANA/APRO4 has been reported to be a tumor suppressor gene in some malignancies. It constitutes important negative regulatory mechanism for Src-mediated signaling, a negative regulator of the cell cycle and inhibits transcription factor E2F1. We report that BTG3 is downregulated in renal cancer and that the mechanism of inactivation is through promoter hypermethylation. Quantitative real-time polymerase chain reaction (PCR) showed that BTG3 was downregulated in cancer tissues and cells. Genistein and 5-aza-2'-deoxycytidine (5Aza-C) induced BTG3 messenger RNA (mRNA) expression in A498, ACHN and HEK-293 renal cell carcinoma (RCC) cell lines. Bisulfite-modified PCR and DNA sequencing results showed complete methylation of BTG3 promoter in tumor samples and cancer cell lines. Genistein and 5Aza-C treatment significantly decreased promoter methylation, reactivating BTG3 expression. Chromatin immunoprecipitation assay revealed that genistein and 5Aza-C increased levels of acetylated histones 3, 4, 2H3K4, 3H3K4 and RNA polymerase II at the BTG3 promoter indicative of active histone modifications. Enzymatic assays showed genistein and 5Aza-C decreased DNA Methyltransferase, methyl-CpG-binding domain 2 activity and increased HAT activity. Cell cycle and 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide cell proliferation assays showed that genistein has antiproliferative effect on cancer cell growth through induction of cell cycle arrest. This is the first report to show that BTG3 is epigenetically silenced in RCC and can be reactivated by genistein-induced promoter demethylation and active histone modification. Genistein had similar effects to that of 5Aza-C, which is a potent demethylating agent with high toxicity and instability. Genistein being a natural, non-toxic, dietary isoflavone is effective in retarding the growth of RCC cells, making it a promising candidate for epigenetic therapy in renal carcinoma.
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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.