scholarly journals Hypermethylation of the Putative Tumor-suppressor Genes DCC, p51/63 and O6-methylguanine-DNA Methyltransferase (MGMT) and Loss of Their Expressions in Cell Lines of Hematological Malignancies

2005 ◽  
Vol 72 (5) ◽  
pp. 270-277 ◽  
Author(s):  
Kazutaka Nakayama ◽  
Koiti Inokuchi ◽  
Kazuo Dan
Keyword(s):  
Tumor Suppressor ◽  
Cell Lines ◽  
Tumor Suppressor Genes ◽  
Dna Methyltransferase ◽  
Hematological Malignancies ◽  
Suppressor Genes ◽  
Methylguanine Dna Methyltransferase ◽  
Putative Tumor Suppressor

scholarly journals MicroRNA-148b and microRNA-152 reactivate tumor suppressor genes through suppression of DNA methyltransferase-1 gene in pancreatic cancer cell lines

2014 ◽  
Vol 15 (4) ◽  
pp. 419-427 ◽  
Author(s):  
Masoumeh Azizi ◽  
Ladan Teimoori-Toolabi ◽  
Mohsen Karimi Arzanani ◽  
Kayhan Azadmanesh ◽  
Pezhman Fard-Esfahani ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Suppressor ◽  
Cell Lines ◽  
Cancer Cell ◽  
Tumor Suppressor Genes ◽  
Dna Methyltransferase ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Dna Methyltransferase 1 ◽  
Suppressor Genes

scholarly journals Promoter Methylation of RASSF1A Associates to Adult Secondary Glioblastomas and Pediatric Glioblastomas

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Jorge Muñoz ◽  
María del Mar Inda ◽  
Paula Lázcoz ◽  
Idoya Zazpe ◽  
Xing Fan ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cell Lines ◽  
Tumor Suppressor Genes ◽  
Promoter Hypermethylation ◽  
Suppressor Genes ◽  
Primary Tumors ◽  
Specific Pcr ◽  
Inactivation Mechanism ◽  
Altered Gene ◽  
Homozygous Deletions

While allelic losses and mutations of tumor suppressor genes implicated in the etiology of astrocytoma have been widely assessed, the role of epigenetics is still a matter of study. We analyzed the frequency of promoter hypermethylation by methylation-specific PCR (MSP) in five tumor suppressor genes (PTEN, MGMT, RASSF1A, p14ARF, and p16INK4A), in astrocytoma samples and cell lines. RASSF1A was the most frequently hypermethylated gene in all grades of astrocytoma samples, in cell lines, and in adult secondary GBM. It was followed by MGMT. PTEN showed a slight methylation signal in only one GBM and one pilocytic astrocytoma, and in two cell lines; while p14ARF and p16INK4A did not show any evidence of methylation in primary tumors or cell lines. In pediatric GBM, RASSF1A was again the most frequently altered gene, followed by MGMT; PTEN, p14 and p16 showed no alterations. Lack or reduced expression of RASSF1A in cell lines was correlated with the presence of methylation. RASSF1A promoter hypermethylation might be used as a diagnostic marker for secondary GBM and pediatric GBM. Promoter hypermethylation might not be an important inactivation mechanism in other genes like PTEN, p14ARF and p16INK4A, in which other alterations (mutations, homozygous deletions) are prevalent.

Putative Tumor Suppressor Genes EGR1 and BRSK1 Are Mutated in Gastric and Colorectal Cancers

Oncology ◽  
2016 ◽  
Vol 91 (5) ◽  
pp. 289-294 ◽  
Author(s):  
Eun Ji Choi ◽  
Nam Jin Yoo ◽  
Min Sung Kim ◽  
Chang Hyeok An ◽  
Sug Hyung Lee
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Colorectal Cancers ◽  
Suppressor Genes ◽  
Putative Tumor Suppressor

scholarly journals Targeting DNA methylation for treating triple-negative breast cancer

2019 ◽  
Vol 20 (16) ◽  
pp. 1151-1157 ◽  
Author(s):  
Jia Yu ◽  
Jacqueline Zayas ◽  
Bo Qin ◽  
Liewei Wang
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Tumor Suppressor ◽  
Triple Negative Breast Cancer ◽  
Targeted Therapies ◽  
Tumor Suppressor Genes ◽  
Dna Methyltransferase ◽  
Triple Negative ◽  
Suppressor Genes ◽  
Dna Methyltransferase Inhibitors

Triple-negative breast cancer (TNBC) accounts for 15–20% of all invasive breast cancers and tends to have aggressive histological features and poor clinical outcomes. Unlike, estrogen receptor- or HER2-positive diseases, TNBC patients currently lack the US FDA-approved targeted therapies. DNA methylation is a critical mechanism of epigenetic modification. It is well known that aberrant DNA methylation contributes to the malignant transformation of cells by silencing critical tumor suppressor genes. DNA methyltransferase inhibitors reactivate silenced tumor suppressor genes and result in tumor growth arrest, with therapeutic effects observed in patients with hematologic malignancies. The antitumor effect of these DNA methyltransferase inhibitors has also been explored in solid tumors, especially in TNBC that currently lacks targeted therapies.

Partial deletions of the CDKN2 and MTS2 putative tumor suppressor genes in a myxoid chondrosarcoma

1996 ◽  
Vol 105 (1) ◽  
pp. 77-90 ◽  
Author(s):  
Ashok A. Jagasia ◽  
Joel A. Block ◽  
Manuel O. Diaz ◽  
Tsutomu Nobori ◽  
Steven Gitelis ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Suppressor Genes ◽  
Myxoid Chondrosarcoma ◽  
Putative Tumor Suppressor

Inactivation of tumor suppressor genes and deregulation of the c-myc gene in urothelial cancer cell lines

1995 ◽  
Vol 23 (5) ◽  
pp. 293-300 ◽  
Author(s):  
M.-O. Grimm ◽  
B. J�rgens ◽  
W. A. Schulz ◽  
K. Decken ◽  
D. Makri ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cell Lines ◽  
Cancer Cell ◽  
Tumor Suppressor Genes ◽  
Urothelial Cancer ◽  
Cancer Cell Lines ◽  
Suppressor Genes ◽  
Myc Gene ◽  
Urothelial Cancer Cell

Strategies to Re-Express Epigenetically-Silenced Tumor Suppressor Genes Converge on the Requirement for Inhibition of the Histone Methyltransferase SUV39H1.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3357-3357
Author(s):  
Asha Lakshmikuttyamma ◽  
Stuart Scott ◽  
David P. Sheridan ◽  
John DeCoteau ◽  
Ron Geyer
Keyword(s):  
Tumor Suppressor ◽  
Cell Lines ◽  
Tumor Suppressor Genes ◽  
Fold Increase ◽  
Dna Demethylation ◽  
Dna Hypermethylation ◽  
Suppressor Genes ◽  
Promoter Dna Methylation ◽  
Promoter Dna ◽  
E Cadherin

Abstract Gene silencing mediated by aberrant promoter DNA hypermethylation represents a key mechanism by which tumor suppressor gene expression is silenced in cancer and it is associated with multiple repressive histone modifications. Histone H3 lysine 9 (H3K9) methylation is a key repressive chromatin modification with important implications for regulating cell proliferation, differentiation, and gene expression. SUV39H1 is a methyltransferase that catalyzes the addition of trimethyl groups to H3K9. SUV39H1 is associated with regions of hypermethylated CpG islands, with repressive complexes, such as RB/E2F, and with DNA-binding proteins involved in leukemogenesis, such as AML1 and PML-RAR, where its H3K9 trimethylation activity promotes heterochromatin formation and gene silencing. We studied the requirement of SUV39H1 in the epigenetic silencing of heavily methylated tumor suppressor genes p15INK4B and E-cadherin in acute myeloid leukemia (AML). Treatment of AML cell lines AML193, KG1a, and Kasumi with the DNA methyltransferase (DNMT) inhibitor 5-Aza-2’-deoxycytidine (5-Aza-dC) induces p15INK4B and E-cadeherin re-expression in association with dramatic decreases in p15INK4B and E-cadherin promoter DNA methylation and marked reductions in the levels of SUV39H1 and H3K9 trimethylation at these promoters. Interestingly, treatment of these cell lines with SUV39H1 shRNA, or the SUV39H1 inhibitor chaetocin, also induces p15INK4B and E-cadherin re-expression and H3K9 demethylation, without affecting promoter DNA methylation. Thus, re-expression of hypermethylated tumor suppressors requires histone H3K9 demethylation, which can be achieved indirectly by decreasing the amount of SUV39H1 associated with the promoter using 5-Aza-dC, or directly by inhibiting SUV39H1 expression or activity without requiring promoter DNA demethylation. Furthermore, we found that SUV39H1 shRNA or chaetocin in combination with 5-Aza-dC acts synergistically to re-express epigenetically silenced p15INK4B and E-cadherin in AML cell lines. Treatment of primary human AML blasts obtained from two patients with combinations of 5-Aza-C and chaetocin also results in synergistic re-expression of p15INK4B and E-cadherin (2–6 fold increase with 5-Aza-C or chaetocin treatment vs. 11–14 fold increase with co-treatment). Our study has important implications for developing novel epigenetic therapies of relevance to AML as it suggests that the re-expression of tumor suppressor genes silenced by aberrant promoter DNA hypermethylation converges on the requirement for SUV39H1 and H3K9 methylation inhibition but not promoter DNA demethylation. Our finding that SUV39H1 inhibition may function synergistically with DNMT inhibitors to enhance gene reactivation and chromatin changes also highlights the needs for developing more inhibitors of histone methyltransferases and for performing detailed drug interaction studies to identify the best drug combinations for optimal epigenetic therapies.

Antitumor Activity of Cda-2, An Extract from Unine, in a High-Risk Myelodysplastic Syndrome Cells in Vitro

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5099-5099
Author(s):  
Lin Qiu ◽  
Xiao-dan Wang ◽  
Bing-hong Han ◽  
Zhao-min Zhan ◽  
Zhang Bo-long ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
High Risk ◽  
Tumor Suppressor ◽  
Myelodysplastic Syndrome ◽  
Tumor Suppressor Genes ◽  
Dna Methyltransferase ◽  
Dependent Manner ◽  
Suppressor Genes ◽  
Specific Pcr

Abstract DNA methyltransferase inhibitors (DNMTI), including 5-azacytidine and 5-aza-2′- deoxycytidine, are a new class of epigenetic drug, which exhibit higher response rates in myelodysplastic syndrome (MDS) patients. Cell differentiation agent (CDA-2) is a kind of urine extracts, which contains several DNMTIs. A phase IV clinical trials for MDS showed total response rate is 69.22%. In the present study, we investigated the mechanism of CDA-2 on MDS using high-risk MDS cell line namely MuTz-1. MTT assay results showed that CDA-2 significantly inhibit the cell growth at a dose and time-dependent manner. Flow cytometer anlyasis showed that this growth inhibition was remarkblely associated with cycle arrest in G1-phase, but not associated with apoptosis. In addition, CDA-2 increased the expression of CD11b/CD14, a pair markers representing cell differentiation. we found the spectrum of hypermethylated tumor suppressor genes (TIMP3, CDKN2B, CHFR, CD44, RASSF1, TP73, IGSF4, CDH13 and DAPK) in MuTz-1 cells by Methylation-Specific Multiplex ligation-dependent Probe amplification (MS-MLPA), but the hypermethylation of these genes were remarkable decreased, as well as the expressions of DNA methyltransferase genes DNMT1 and DNMT3B at mRNA and protein level were downregulated in the treatment for 3 days with CDA-2. Also, we used CDA-2 for treatment of three MDS patients, whose several tumor suppressor genes are hypermethylated. After tour weeks of treatment, all the hypermethylation genes were undetected, part of this result was verified by methylation specific PCR (MSP) and bisulphite sequencing. In conclusion, our results demonstrated that CDA-2 may be an effective agent targeting hepermethylated tumor suppressor genes on MDS.

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