Effects of DNA methylation on DNA-binding proteins and gene expression

Täte, P.; Bird, Adrian

doi:10.1016/0959-437x(93)90027-m

Cited by 669 publications

(440 citation statements)

References 43 publications

Supporting

Mentioning

428

Contrasting

Unclassified

Order By: Relevance

“…Deregulation of DNA methyltransferases have been implicated as a potential link to hypermethylation [54]. Some studies suggest that the activity of DNA methyltransferases does not correlate with the hypermethylation of CpGs within a gene [55] yet, others have shown elevated DNA methyltransferases in a subset of patients which exhibit gene hypermethylation [53,56,57].…”

Section: Discussionmentioning

confidence: 99%

Epigenetic silencing contributes to the loss of BRMS1 expression in breast cancer

Metge

Frost

King

et al. 2008

Clin Exp Metastasis

View full text Add to dashboard Cite

Breast Cancer Metastasis Suppressor 1 (BRMS1) suppresses metastasis of human breast cancer, ovarian cancer and melanoma in athymic mice. Studies have also shown that BRMS1 is significantly downregulated in some breast tumors, especially in metastatic disease. However, the mechanisms which regulate BRMS1 expression are currently unknown. Upon examination of the BRMS1 promoter region by methylation specific PCR (MSP) analysis, we discovered a CpG island (−3477 to −2214), which was found to be hypermethylated across breast cancer cell lines. A panel of 20 patient samples analyzed showed that 45% of the primary tumors and 60% of the matched lymph node metastases, displayed hypermethylation of BRMS1 promoter. Furthermore, we found a direct correlation between the methylation status of the BRMS1 promoter in the DNA isolated from tissues, with the loss of BRMS1 expression assessed by immunohistochemistry. There are several studies investigating the mechanism by which BRMS1 suppresses metastasis; however thus far there is no

show abstract

Section: Discussionmentioning

confidence: 99%

Epigenetic silencing contributes to the loss of BRMS1 expression in breast cancer

Metge

Frost

King

et al. 2008

Clin Exp Metastasis

View full text Add to dashboard Cite

show abstract

“…It is known that inactivating mutations occur during the replication of Moloney murine leukemia virus-based vectors. 39 Hypermethylation of transcriptional regulatory elements may also be responsible for a decreased level of tk expression, 40 although the neo expression is not shut down. These prodrug-resistant cells might be partially responsible for the incomplete tumor regression and tumor recurrence observed in mice.…”

Section: Discussionmentioning

confidence: 99%

Comparative in vitro and in vivo cytotoxic activity of (E)-5-(2-bromovinyl)-2′-deoxyuridine (BVDU) and its arabinosyl derivative, (E)-5-(2-bromovinyl)-1-β-D-arabinofuranosyluracil (BVaraU), against tumor cells expressing either the Varicella zoster or the Herpes simplex virus thymidine kinase

Grignet¹,

Cool²,

Baudson³

et al. 2000

Cancer Gene Ther

View full text Add to dashboard Cite

The inhibitory effects of (E)-5-(2-bromovinyl)-2Ј-deoxyuridine (BVDU) and its arabinosyl derivative (E)-5-(2-bromovinyl)-1-␤-Darabinofuranosyluracil (BVaraU) on the growth of both MDA-MB-435 human breast carcinoma and 9L rat gliosarcoma cells expressing the thymidine kinase (tk)-encoding gene of the Varicella zoster virus (VZV) or the Herpes simplex virus (HSV) were evaluated. In vitro, BVDU and BVaraU effectively killed both cell types expressing VZVtk, with 50% inhibitory concentration values ranging from 0.06 to 0.4 M, whereas ganciclovir (GCV) lacked activity. On HSVtk ϩ cells, BVDU had high cytotoxic activity, with 50% inhibitory concentration values that were similar to those of GCV, whereas BVaraU was inactive. In vivo, BVDU applied intraperitoneally caused a 50% tumor growth inhibition in nude mice inoculated subcutaneously with VZVtk ϩ as well as HSVtk ϩ mammary tumor cells. In mice and at variance with the in vitro results, BVaraU had very little activity against the VZVtk ϩ mammary cells; GCV had the highest activity on the HSVtk ϩ cells, resulting in a 50% eradication of the tumors. With the 9L rat gliosarcoma model, the VZVtk/BVDU system completely failed to inhibit the development of VZVtk ϩ glioma tumors induced subcutaneously in syngeneic rats, although BVDU had a similar 45-minute half-life in both rats and mice. Factors other than degradation of the prodrug and related to the mode of action of these analogs are possibly involved in the observed discrepancies between the in vitro and in vivo results. Cancer Gene Therapy (2000) 7, 215-223

show abstract

“…Two types of mechanism could be involved in silencing genes by DNA methylation. CpG methylation can down-regulate gene expression by preventing the binding of transcription factors to their recognition sequences or through repressor molecules that bind to methylated DNA (22,23). The methyl-CpG binding proteins (MBD), a family of vertebrate proteins, bind to methylated DNA in any sequence context (22); for some members of this family it has been shown that the binding of such proteins represses gene expression at a distance (24).…”

mentioning

confidence: 99%

Regional methylation of the 5' end CpG island of BRCA1 is associated with reduced gene expression in human somatic cells

Magdinier¹

2000

The FASEB Journal

View full text Add to dashboard Cite

Effects of DNA methylation on DNA-binding proteins and gene expression

Cited by 669 publications

References 43 publications

Epigenetic silencing contributes to the loss of BRMS1 expression in breast cancer

Epigenetic silencing contributes to the loss of BRMS1 expression in breast cancer

Comparative in vitro and in vivo cytotoxic activity of (E)-5-(2-bromovinyl)-2′-deoxyuridine (BVDU) and its arabinosyl derivative, (E)-5-(2-bromovinyl)-1-β-D-arabinofuranosyluracil (BVaraU), against tumor cells expressing either the Varicella zoster or the Herpes simplex virus thymidine kinase

Regional methylation of the 5' end CpG island of BRCA1 is associated with reduced gene expression in human somatic cells

Contact Info

Product

Resources

About