ArticleOncogene2007
Epigenetic inactivation of the tissue inhibitor of metalloproteinase-2 (TIMP-2) gene in human prostate tumors.
Article in Oncogene, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 2 syntheses or guidelines pooled it, 95 citations in OpenAlex.
- The Role of the Metzincin Superfamily in Prostate Cancer Progression: A Systematic-Like Review.International journal of molecular sciences · 2021Pooled it
- Modeling human prostate cancer progression in vitro.Carcinogenesis · 2019Pooled it
- MeCP2 functions as a DNA methylation reader in immune homeostasis and cancer.Frontiers in epigenetics and epigenomics · 2026Review
- DNA Methylation in Prostate Cancer: Clinical Implications and Potential Applications.Cancer medicine · 2025Review
- Nature's Elixir for Cancer Treatment: Targeting Tumor-induced Neovascularization.Current medicinal chemistry · 2024Review
- The Contribution of Tissue Inhibitor of Metalloproteinase-2 Genotypes to Breast Cancer Risk in Taiwan.Life (Basel, Switzerland) · 2023Article
- The Epigenetic Reader Methyl-CpG-Binding Protein 2 (MeCP2) Is an Emerging Oncogene in Cancer Biology.Cancers · 2023Review
- Article
- TDG suppresses the migration and invasion of human colon cancer cells via the DNMT3A/TIMP2 axis.International journal of biological sciences · 2022Article
- The Biology and Function of Tissue Inhibitor of Metalloproteinase 2 in the Lungs.Pulmonary medicine · 2022Review
- Epigenetic Regulations of Perineural Invasion in Head and Neck Squamous Cell Carcinoma.Frontiers in genetics · 2022Review
- The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases.International journal of molecular sciences · 2020Review
- Selected Matrix Metalloproteinases (MMP-2, MMP-7) and Their Inhibitor (TIMP-2) in Adult and Pediatric Cancer.Diagnostics (Basel, Switzerland) · 2020Review
- Sinomenine Inhibits Migration and Invasion of Human Lung Cancer Cell through Downregulating Expression of miR-21 and MMPs.International journal of molecular sciences · 2020Article
- Review
- Differential gene methylation patterns in cancerous and non‑cancerous cells.Oncology reports · 2019Article
- DNA Methylation Readers and Cancer: Mechanistic and Therapeutic Applications.Frontiers in oncology · 2019Review
- Review
- A survey of metastasis suppressors in Metazoa.Laboratory investigation; a journal of technical methods and pathology · 2018Review
- Ras-related protein Rap2c promotes the migration and invasion of human osteosarcoma cells.Oncology letters · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Gene silencing via CpG island methylation in the promoter region is one of the mechanisms by which tumor suppressor genes are inactivated in human cancers. Previous studies have shown that the tissue inhibitors of metalloproteinases (TIMP)-2 gene, which is an endogenous inhibitor of matrix metalloproteinases involved in cell invasion and tumorigenesis, is downregulated or silenced in a variety of human cancer cell lines. Here, we investigated the mechanism underlying TIMP-2 expression in prostate cancer cell lines and primary prostate tumor samples. We observed a strong correlation between promoter hypermethylation and lost expression of TIMP-2 gene, which was supported by other results demonstrating that promoter demethylation by 5-aza-2'-deoxycytidine and trichostatin A reactivated TIMP-2 and restored its expression in TIMP-2-silenced metastatic prostate cell lines. These results were further substantiated by a chromatin immunoprecipitation assay, showing the preferential binding of MeCP2 to methylated CpG island in TIMP-2-silenced metastatic prostate cell lines. In vitro Matrigel invasion assays showed that re-expression of TIMP-2 after a combined treatment with 5-aza and trichostatin-A in metastatic prostate cells resulted in a significant reduction of tumor cell invasion. Furthermore, CpG methylation of TIMP-2 promoter was also shown in primary prostate tumors that expressed decreased TIMP-2 protein levels. These results suggest that the downregulation of the TIMP-2 gene is associated with promoter methylation and that this may play an important role in prostate cancer progression during the invasive and metastatic stages of the disease.
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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.