Methylation in the p53 promoter in epithelial ovarian cancer

Chmelařová, Marcela; Křepinská, E; Špaček, Jiří; Laco, Ján; Beránek, M.; Palička, Vladimír

doi:10.1007/s12094-012-0894-z

Cited by 51 publications

(32 citation statements)

References 13 publications

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“…Studies of methylation and TP53 in breast cancer are currently limited, although hypermethylation has been reported in epithelial ovarian and cervical cancers [32,33]. These two studies examined a region of TP53 that is encompassed by six HM450K CpG probes between chr17:7,590,728 and chr17:7,591,011.…”

Section: Discussionmentioning

confidence: 99%

Methylation of Breast Cancer Predisposition Genes in Early-Onset Breast Cancer: Australian Breast Cancer Family Registry

et al. 2016

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DNA methylation can mimic the effects of both germline and somatic mutations for cancer predisposition genes such as BRCA1 and p16INK4a. Constitutional DNA methylation of the BRCA1 promoter has been well described and is associated with an increased risk of early-onset breast cancers that have BRCA1-mutation associated histological features. The role of methylation in the context of other breast cancer predisposition genes has been less well studied and often with conflicting or ambiguous outcomes. We examined the role of methylation in known breast cancer susceptibility genes in breast cancer predisposition and tumor development. We applied the Infinium HumanMethylation450 Beadchip (HM450K) array to blood and tumor-derived DNA from 43 women diagnosed with breast cancer before the age of 40 years and measured the methylation profiles across promoter regions of BRCA1, BRCA2, ATM, PALB2, CDH1, TP53, FANCM, CHEK2, MLH1, MSH2, MSH6 and PMS2. Prior genetic testing had demonstrated that these women did not carry a germline mutation in BRCA1, ATM, CHEK2, PALB2, TP53, BRCA2, CDH1 or FANCM. In addition to the BRCA1 promoter region, this work identified regions with variable methylation at multiple breast cancer susceptibility genes including PALB2 and MLH1. Methylation at the region of MLH1 in these breast cancers was not associated with microsatellite instability. This work informs future studies of the role of methylation in breast cancer susceptibility gene silencing.

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Section: Discussionmentioning

confidence: 99%

Methylation of Breast Cancer Predisposition Genes in Early-Onset Breast Cancer: Australian Breast Cancer Family Registry

et al. 2016

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“…[39][40][41] Recent studies revealed that global DNA hypomethylation and hypermethylation are both involved in several physiological processes, including tumorigenesis and CKD. [42][43][44] Based on a vast amount of findings, genes, which may be regulated by DNA methylation, are known to possess CpG islands within proximal promoter regions. We previously reported that the expression of EC-SOD in basal human monocytic THP-1 cells was silenced, and attributed this to CpG hypermethylation within its promoter region.…”

Section: Discussionmentioning

confidence: 99%

CoCl<sub>2</sub> Decreases EC-SOD Expression through Histone Deacetylation in COS7 Cells

Hattori

Kamiya

Hara

et al. 2016

Biological & Pharmaceutical Bulletin

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Extracellular-superoxide dismutase (EC-SOD), one of the SOD isozymes, is negatively regulated under hypoxic conditions, and decreases in its expression may exacerbate vascular diseases. Moreover, epigenetics, such as DNA methylation and histone modifications, are known to play a critical role in the progression of cancer, type 2 diabetes, and atherosclerosis. We previously investigated the involvement of reactive oxygen species (ROS) and p38 mitogen-activated protein kinase (MAPK) in decreases in EC-SOD expression in hypoxic COS7 cells; however, the role of epigenetics in this process currently remains unknown. In the present study, we demonstrated that the hypoxia mimetic cobalt chloride (CoCl 2 ) decreased histone acetylation levels, and a pretreatment with 4-phenyl butyric acid (PBA), an inhibitor of histone deacetylase, significantly suppressed CoCl 2 -elicited histone deacetylation and decreases in EC-SOD. We found that CoCl 2 -elicited decreases in EC-SOD were accompanied by reductions in histone H3 acetylation levels within its promoter region. Furthermore, luteolin, a well-known flavonoid, significantly suppressed the CoCl 2 -elicited accumulation of ROS, p38-MAPK activation, and histone deacetylation. Collectively, the results of the present study showed for the first time that CoCl 2 decreases the expression of EC-SOD through its deacetylation and luteolin may be one of the seed compounds that maintain redox homeostasis, even under hypoxic conditions.

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“…[42][43][44][45] Alternatively, there is an acute DNA-repair related event after Tet1 overexpression, which triggers the phosphorylation and up-regulation of p53 as p53 is quickly up-regulated after DNA damage triggered by UV or ionizing irradiation. 46 base excision repair was shown to be required for the completion of TET-mediated demethylation process, 29 48 49 we decided to check the association of p53 increase with DNA-damage signaling pathways.…”

Section: Phospho-p53 (Ser15) Is Elevated By Dna-pk Phosphorylation Inmentioning

confidence: 99%

TET1 Exerts Its Tumor Suppressor Function by Interacting with p53-EZH2 Pathway in Gastric Cancer

Fu¹,

Ma²,

Lu³

et al. 2014

Journal of Biomedical Nanotechnology

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TET1 protein is reported to suppress cancer invasion and metastasis in prostate and breast cancer while EZH2, a polycomb group protein, has been identified as an oncogene in many types of cancers including gastric cancer. Here we report that there is an inverse relation of the expression pattern of TET1 and EZH2 in both normal gastric mucosa and gastric cancer. In gastric mucosa, EZH2 is selectively expressed in the proliferating neck cells while TET1 and 5-hydroxymethyl-cytosine (5-hmc) exhibit very low expression in the neck cells. In contrast, TET1 and 5-hmc expression is high in gastric glandular epithelium while EZH2 expression is absent in this cell population. On the other hand, in proliferating Ki67-positive gastric cancer cells, EZH2 is highly expressed while TET1 and 5-hmc expression is significantly down-regulated. When the mouse homologue of human TET1 protein Tet1 is overexpressed in a gastric cancer cell line MGC-803, we observed the dramatically down-regulation of EZH2 in one-third of the Tet1 overexpressed cells. In addition, Tet1 overexpressing cells also lost the H3K27 trimethylation mark and the cell proliferation protein Ki67. Furthermore, Tet1 overexpression induced p53 tumor suppressor protein. The increase of p53 protein level is accompanied by the phosphorylation of p53 by activated DNA-PK. Together, these results suggested a mechanism by which TET1 suppresses cancer formation by coupling DNA demethylation with DNA-PK activation of p53 and suppression of oncogenic protein EZH2. Conversely, loss of TET1 and 5-hmc expression might contribute to EZH2 up-regulation during gastric cancer development.

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Methylation in the p53 promoter in epithelial ovarian cancer

Abstract: These results indicate that methylation in p53 promoter region may play an important role in carcinogenesis of ovarian cancer and could potentially be used in screening of ovarian cancer, and may have implications for future chemotherapy based on epigenetic changes.

Cited by 51 publications

References 13 publications

Methylation of Breast Cancer Predisposition Genes in Early-Onset Breast Cancer: Australian Breast Cancer Family Registry

Methylation of Breast Cancer Predisposition Genes in Early-Onset Breast Cancer: Australian Breast Cancer Family Registry

CoCl<sub>2</sub> Decreases EC-SOD Expression through Histone Deacetylation in COS7 Cells

TET1 Exerts Its Tumor Suppressor Function by Interacting with p53-EZH2 Pathway in Gastric Cancer

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