Kidney, Brain, and Other Human Cancers Gene Suggests a Suppressor Role in Metalloproteinase-3 Methylation-associated Silencing of the Tissue Inhibitor of Updated Version
نویسندگان
چکیده
Tissue inhibitor of metalloproteinase-3 (TIMP-3) antagonizes matrix metalloproteinase activity and can suppress tumor growth, angiogenesis, invasion, and metastasis. Loss of TIMP-3 has been related to the acquisition of tumorigenesis. Herein, we show that TIMP-3 is silenced in association with aberrant promoter-region methylation in cell lines derived from human cancers. TIMP-3 expression was restored after 5-aza-2*deoxycytidine-mediated demethylation of the TIMP-3 proximal promoter region. Genomic bisulfite sequencing revealed that TIMP-3 silencing was related to the overall density of methylation and that discrete regions within the TIMP-3 CpG island may be important for the silencing of this gene. Aberrant methylation of TIMP-3 occurred in primary cancers of the kidney, brain, colon, breast, and lung, but not in any of 41 normal tissue samples. The most frequent TIMP-3 methylation was found in renal cancers, which originate in the tissue that normally expresses the highest TIMP-3 levels. This methylation correlated with a lack of detectable TIMP-3 protein in these tumors. Together, these data show that methylation-associated inactivation of TIMP-3 is frequent in many human tumors.
منابع مشابه
E-cadherin Promoter Methylation Comparison and Correlation with the Pathological Features of the Squamous Cell Carcinoma of Esophagus in the High Risk Region
E-cadherin is among tumor suppressor genes which mostly subjects to the down-regulation in squamous cell carcinoma of esophagus (SCCE). The gene is tightly associated with the tumor invasion and metastasis in multiple human cancers, especially SCCE. CpG islands’ methylation in the promoter region of E-cadherin is among the mechanisms that have been suggested for the E-cadherin silencing, howeve...
متن کاملاپیژنتیک سرطان پستان: مقاله مروری
Stable molecular changes during cell division without any change in the sequence of DNA molecules is known as epigenetic. Molecular mechanisms involved in this process, including histone modifications, methylation of DNA, protein complex and RNA antisense. Cancer genome changes happen through a combination of DNA hypermethylation, long-term epigenetic silencing with heterozygosis loss and genom...
متن کاملHypermethylation of E-Cadherin and Estro-gen Receptor- Gene Promoter and Its Association with Clinicopathological Features of Breast Cancer in Iranian Patients
Background: Aberrant methylation of cytosine-guanine dinucleotide islands leads to inactivation of tumor suppressor genes in breast cancer. Tumor suppressor genes are unmethylated in normal tissue and often become hypermethylated during tumor formation, leading to gene silencing. We investigated the association between E-cadherin (CDH1) and estrogen receptor-α (ESRα) gene promoter methylation a...
متن کاملTwo Steps Methylation Specific PCR for Assessment of APC Promoter Methylation in Gastric Adenocarcinoma
Gastric Cancer (GC) is the second most common cancer in the world and a leading cause of cancer-related mortality. Methylation of promoter CpG islands (CGIs) belonging to tumor suppressor genes causes transcriptional silencing of their corresponding genes leading to carcinogenesis and other disorders. Adenomatous Polyposis Coli (APC) a tumor suppressor gene is inactivated by methylation of prom...
متن کاملDNA Methylation and the Expression of the Tumor-Suppressor Genes Protocadherin-10 and Reprimo in Pediatric Acute Lymphoblastic Leukemia
Background: Acute lymphoblastic leukemia (ALL) is the most prevalent hematologic malignancy among children. DNA methylation is well known to play a role in the initiation and progression of cancer. This research aimed to characterize the epigenetic inactivation and gene expression of Protocadherin-10 (PCDH10) and Reprimo (RPRM) in pediatric acute lymphoblastic leukemia, which is associated with...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره شماره
صفحات -
تاریخ انتشار 1999