Abstract:
:p125 is one of four subunits of human DNA polymerases - DNA Pol δ as well as one of p53 target protein encoded by POLD1. However, the function and significance of p125 and the role that p53 plays in regulating p125 expression are not fully understood in breast cancer. Tissue sections of human breast cancer obtained from 70 patients whose median age was 47.6 years (range: 38-69 years) with stage II-III breast cancer were studied with normal breast tissue from the same patients and two human breast cell lines (MCF-7 and MCF-10A). p53 expression levels were reduced, while p125 protein expression was increased in human breast cancer tissues and cell line detected by Western blot and quantitative reverse transcriptase-polymerase chain reaction. The methylation level of the POLD1 gene promoter was greater in breast cancer tissues and cells when compared with normal tissues and cells. In MCF-7 cell model, p53 overexpression caused a decrease in the level of p125 protein, while the methylation level of the p125 gene promoter was also inhibited by p53 overexpression. To further investigate the regulating mechanism of p53 on p125 expression, our study focused on DNA methyltransferase 1 (DNMT1) and transcription factor Sp1. Both DNMT1 and Sp1 protein expression were reduced when p53 was overexpressed in MCF-7 cells. The Sp1 binding site appears to be important for DNMT1 gene transcription; Sp1 and p53 can bind together, which means that DNMT1 gene expression may be downregulated by p53 through binding to Sp1. Because DNMT1 methylation level of the p125 gene promoter can affect p125 gene transcription, we propose that p53 may indirectly regulate p125 gene promoter expression through the control of DNMT1 gene transcription. In conclusion, the data from this preliminary study have shown that p53 inhibits the methylation of p125 gene promoter by downregulating the activities of Sp1 and DNMT1 in breast cancer.
journal_name
Onco Targets Therjournal_title
OncoTargets and therapyauthors
Zhang L,Yang W,Zhu X,Wei Cdoi
10.2147/OTT.S98713subject
Has Abstractpub_date
2016-03-10 00:00:00pages
1351-60issn
1178-6930pii
ott-9-1351journal_volume
9pub_type
杂志文章abstract::The study aimed to investigate the difference of setup errors on different registration in the treatment of nasopharyngeal carcinoma based on weekly cone-beam computed tomography (CBCT). Thirty nasopharyngeal cancer patients scheduled to undergo intensity-modulated radiotherapy (IMRT) were prospectively enrolled in th...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S87159
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abstract:Purpose:Circular RNAs (circRNAs) have been found to regulate several human tumors. The present study was to explore the mechanism of hsa_circ_0087862 in regulating non-small cell lung cancer (NSCLC). Methods:Totally 102 NSCLC cases were enrolled. NCI-H1359 and A549 cells were transfected. Cells viability, apoptosis, m...
journal_title:OncoTargets and therapy
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journal_title:OncoTargets and therapy
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doi:10.2147/OTT.S86502
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journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S62561
更新日期:2014-06-20 00:00:00
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journal_title:OncoTargets and therapy
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doi:10.2147/OTT.S101067
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abstract::Recently, "ipilimumab," an anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) monoclonal antibody, has been demonstrated to improve overall survival in metastatic melanoma. "CTLA-4" is an immune-checkpoint molecule that downregulates pathways of T-cell activation. Ipilimumab, by targeting CTLA-4, is able to remove the CTL...
journal_title:OncoTargets and therapy
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journal_title:OncoTargets and therapy
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doi:10.2147/OTT.S86743
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journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
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journal_title:OncoTargets and therapy
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journal_title:OncoTargets and therapy
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journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
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journal_title:OncoTargets and therapy
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doi:10.2147/OTT.S84938
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journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
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journal_title:OncoTargets and therapy
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journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S259895
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journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S130481
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journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S157759
更新日期:2018-05-09 00:00:00
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journal_title:OncoTargets and therapy
pub_type:
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journal_title:OncoTargets and therapy
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更新日期:2016-06-01 00:00:00
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journal_title:OncoTargets and therapy
pub_type: 撤回出版物
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journal_title:OncoTargets and therapy
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journal_title:OncoTargets and therapy
pub_type:
doi:10.2147/OTT.S236728
更新日期:2020-02-03 00:00:00
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journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S106513
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journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S161996
更新日期:2018-04-24 00:00:00
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journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S194745
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journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S104767
更新日期:2017-02-28 00:00:00
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journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S172149
更新日期:2018-09-17 00:00:00
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journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S249527
更新日期:2020-06-08 00:00:00
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journal_title:OncoTargets and therapy
pub_type: 杂志文章
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