DNA methylation and apoptosis

Gopisetty, Gopal; Ramachandran, K.; Singal, Rakesh

doi:10.1016/j.molimm.2005.11.010

Cited by 99 publications

(80 citation statements)

References 107 publications

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“…11 CpG islands remain unmethylated in housekeeping genes and methylated or silenced in other genes. 12 DNA is methylated by DNA methyltransferases (DNMTs), which transfer the methyl group from Sadenosylmethionine (SAM) to generate patterns of genomic methylation that silence genes [13][14][15] ( Figure 1). The DNMTs known to date are DNMT1, DNMT2, DNMT3a, DNMT3b, and DNMT3L.…”

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confidence: 99%

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DNA methylation in breast and colorectal cancers

2007

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DNA methylation is one of several epigenetic changes observed in cells. Aberrant methylation of tumor suppressor genes, proto-oncogenes, and vital cell cycle genes has led many scientists to investigate the underlying cellular mechanisms of DNA methylation under normal and pathological conditions. Although DNA methylation is necessary for normal mammalian embryogenesis, both hypo-and hypermethylation of DNA are frequently observed in carcinogenesis and other pathological disorders. DNA hypermethylation silences the transcription of many tumor suppressor genes, resulting in immortalization of tumor cells. The reverse process, demethylation and restoration of normal functional expression of genes, is augmented by DNA methylation inhibitors. Recent studies suggest that DNA hypomethylation may also control gene expression and chromosomal stability. However, the roles of and relationship between hypomethylation and hypermethylation are not well understood. This review provides a brief overview of the mechanism of DNA methylation, its relationship to extrinsic stimulation including dietary intake and aging, and of abnormally methylated DNA in breast and colorectal cancers, which could be used as prognostic and diagnostic markers.

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confidence: 99%

“…The DNMTs known to date are DNMT1, DNMT2, DNMT3a, DNMT3b, and DNMT3L. 15,16 All methyltransferases have homology and different functions. DNMT1 maintains established methylation patterns in hemi-methylated genes by copying methylation patterns from the parent strand to the daughter and is expressed during the S-phase.…”

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confidence: 99%

DNA methylation in breast and colorectal cancers

2007

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“…Apoptosis or programmed cell death contributes to the maintenance of cell homeostasis by enabling the removal of physiologically defective cells (4). Dysregulation of apoptosis leads to the survival of defective cells and can contribute to the development of cancer (24).…”

Section: Discussionmentioning

confidence: 99%

“…Aberrant promoter methylation plays a key role in genetic imprinting, developmental abnormalities, X-chromosome inactivation, and cancer biology (3,4). Epigenetic silencing of tumor suppressor genes by promoter DNA hypermethylation is a general characteristic of human cancers (5,6).…”

Section: Introductionmentioning

confidence: 99%

Promoter Methylation and mRNA Expression of APAF-1 Gene in Breast Cancer

Eskandari-Nasab

Hashemi

2016

Gene Cell Tissue

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Background: Apoptosis protease-activating factor-1 (APAF-1) is an important tumor suppressor gene, which plays a central function in DNA damage-induced apoptosis. The present study aimed to examine the epigenetic regulation of APAF-1 in breast cancer to gain a better understanding of tumor biology. Methods:The promoter methylation of APAF-1 gene was determined by methylation-specific polymerase chain reaction (MS-PCR) method, using 63 paraffin-embedded breast tumors and their corresponding normal tissues as the control tissue samples. Expression analysis was performed on all tissue samples, using quantitative PCR (qPCR) method.Results: Significant down-regulation was observed for APAF-1 expression among tumor tissues, compared to the control group (P = 0.011). APAF-1 promoter hypermethylation was more frequent in breast tumors in comparison with normal tissues (57% vs. 21%; P = 0.001) and was correlated with gene mRNA level (P < 0.05). Methylation level increased from the primary to the advanced stage of the disease (P = 0.001), which suggests the possible role of APAF-1 methylation in disease progression. Conclusions:Methylation is an important epigenetic factor which might contribute to the down-regulation of APAF-1 gene in breast tumor tissues.

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“…The pattern of altered gene expression or epigenetic change is important in common malignancies (8). DNA is methylated by DNA methyltransferases (DNMTs), which transfer the methyl group from S-adenosylmethionine (SAM) to generate patterns of genomic methylation that silence gene expression (9)(10)(11). To date, the following DNMTs have been identified: DNMT1, DNMT2, DNMT3a, DNMT3b and DNMT3L (12).…”

Section: Introductionmentioning

confidence: 99%

Arsenic trioxide re-sensitizes ERα-negative breast cancer cells to endocrine therapy by restoring ERα expression in vitro and in vivo

Zhang

Wang²,

Fan³

et al. 2011

Oncol Rep

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Abstract. Approximately one-third of breast cancers lack estrogen receptor α (ERα) because of the hypermethylation of the CpG island in the receptor's promoter. These tumors are associated with poorer histological differentiation, a higher growth fraction, are rarely responsive to endocrine therapy and have a worse clinical outcome. Thus, re-expression of ERα in ERα-negative breast cancers may restore the sensitivity of antiestrogen therapy. The ERα-negative breast cancer cell line MDA-MB-435s was treated with different concentrations of arsenic trioxide (As 2 O 3 ). MS-PCR was used to detect the change in the methylation status of ERα. RT-PCR, immunohistochemistry and Western blot analyses were used to detect changes in the mRNA and protein expression of DNA methyltransferase-1 (DNMT1) and ERα. Cell proliferation was examined using the MTT assay. A xenograft model in nude mice was used to further examine the results we observed in vitro. The ERα gene was demethylated after As 2 O 3 treatment of MDA-MB-435s cells. RT-PCR, immunohistochemistry and Western blot analyses revealed that DNMT1 expression was inhibited and ERα was re-expressed in a concentrationdependent manner after As 2 O 3 treatment. The MTT assay showed that cell proliferation was significantly suppressed after exposure to different concentrations of As 2 O 3 . Addition of tamoxifen (TAM) further suppressed levels of cell proliferation. In vivo, the xenograft tumor volumes of As 2 O 3 -treated mice were smaller than those observed in untreated and TAM-treated mice. Treatment with a combination of As 2 O 3 + TAM resulted in further suppression. As 2 O 3 can act as a demethylation agent to restore ERα expression in ERα-negative breast cancer cells and re-sensitize these cells to endocrine therapy in vitro and in vivo.

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DNA methylation and apoptosis

Cited by 99 publications

References 107 publications

DNA methylation in breast and colorectal cancers

DNA methylation in breast and colorectal cancers

Promoter Methylation and mRNA Expression of APAF-1 Gene in Breast Cancer

Arsenic trioxide re-sensitizes ERα-negative breast cancer cells to endocrine therapy by restoring ERα expression in vitro and in vivo

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