scholarly journals DNA methyltransferase 1 expression and promoter methylation of E-cadherin in mucoepidermoid carcinoma

Cancer ◽  
2005 ◽  
Vol 104 (5) ◽  
pp. 1013-1021 ◽  
Author(s):  
Yi-Shing Shieh ◽  
Shine-Gwo Shiah ◽  
Hao-Hsuan Jeng ◽  
Herng-Sheng Lee ◽  
Cheng-Wen Wu ◽  
...  
Keyword(s):  
Promoter Methylation ◽  
Mucoepidermoid Carcinoma ◽  
Dna Methyltransferase ◽  
Dna Methyltransferase 1 ◽  
E Cadherin ◽  
Methyltransferase 1

scholarly journals Induction of altered epigenetic regulation of the hepatic glucocorticoid receptor in the offspring of rats fed a protein-restricted diet during pregnancy suggests that reduced DNA methyltransferase-1 expression is involved in impaired DNA methylation and changes in histone modifications

2007 ◽  
Vol 97 (6) ◽  
pp. 1064-1073 ◽  
Author(s):  
Karen A. Lillycrop ◽  
Jo L. Slater-Jefferies ◽  
Mark A. Hanson ◽  
Keith M. Godfrey ◽  
Alan A. Jackson ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Histone Modifications ◽  
Epigenetic Regulation ◽  
Promoter Methylation ◽  
Dna Methyltransferase ◽  
Metabolic Phenotype ◽  
Dna Methyltransferase 1 ◽  
Gene Promoters ◽  
Dnmt1 Expression ◽  
Methyltransferase 1

Prenatal nutritional constraint induces an altered metabolic phenotype in the offspring which in humans confers an increased risk of non-communicable disease. Feeding a protein-restricted (PR) diet to pregnant rats causes hypomethylation of specific gene promoters in the offspring and alters the phenotype. We investigated how altered epigenetic regulation of the hepatic glucocorticoid receptor (GR) 110 promoter is induced in the offspring. Rats were fed a control (180 g casein/kg) or a PR (90 g casein/kg) diet throughout pregnancy, and chow during lactation. Offspring were killed at postnatal day 34 (n 5 per maternal dietary group). Methylation-sensitive PCR showed that GR110 promoter methylation was 33 % lower (P < 0·001) and GR expression 84 % higher (P < 0·05) in the PR offspring. Reverse transcription–PCR showed that DNA methyltransferase-1 (Dnmt1) expression was 17 % lower (P < 0·05) in PR offspring, while Dnmt3a/b and methyl binding domain protein-2 expression was not altered. Thus hypomethylation of the GR110 promoter may result from lower capacity to methylate hemimethylated DNA during mitosis. Histone modifications which facilitate transcription were increased at the GR110 promoter (147–921 %, P < 0·001), while those that suppress methylation were decreased (54 %, P < 0·01) or similar to controls. In human umbilical cord (n 15), there was a 2-fold difference between the highest and lowest level of GR1-CTotal promoter methylation. Dnmt1, but not Dnmt3a, expression predicted 49 % (P = 0·003) of the variation in GR1-CTotal promoter methylation. These findings suggest that induction in the offspring of altered epigenetic regulation of the hepatic GR110 promoter, and hence metabolic phenotype, may be due to reduced Dnmt1 expression.

scholarly journals RX-3117 (Fluorocyclopentenyl-Cytosine)-Mediated Down-Regulation of DNA Methyltransferase 1 Leads to Protein Expression of Tumor-Suppressor Genes and Increased Functionality of the Proton-Coupled Folate Carrier

2020 ◽  
Vol 21 (8) ◽  
pp. 2717 ◽  
Author(s):  
Dzjemma Sarkisjan ◽  
Joris R. Julsing ◽  
Btissame El Hassouni ◽  
Richard J. Honeywell ◽  
Ietje Kathmann ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Protein Expression ◽  
Tumor Suppressor Genes ◽  
Dna Methyltransferase ◽  
Functional Assay ◽  
Dna Methyltransferase 1 ◽  
Suppressor Genes ◽  
Resistant Variant ◽  
E Cadherin ◽  
Methyltransferase 1

(1) Background: RX-3117 (fluorocyclopentenyl-cytosine) is a cytidine analog that inhibits DNA methyltransferase 1 (DNMT1). We investigated the mechanism and potential of RX-3117 as a demethylating agent in several in vitro models. (2) Methods: we used western blotting to measure expression of several proteins known to be down-regulated by DNA methylation: O6-methylguanine-DNA methyltransferase (MGMT) and the tumor-suppressor genes, p16 and E-cadherin. Transport of methotrexate (MTX) mediated by the proton-coupled folate transporter (PCFT) was used as a functional assay. (3) Results: RX-3117 treatment decreased total DNA-cytosine-methylation in A549 non-small cell lung cancer (NSCLC) cells, and induced protein expression of MGMT, p16 and E-cadherin in A549 and SW1573 NSCLC cells. Leukemic CCRF-CEM cells and the MTX-resistant variant (CEM/MTX, with a deficient reduced folate carrier) have a very low expression of PCFT due to promoter hypermethylation. In CEM/MTX cells, pre-treatment with RX-3117 increased PCFT-mediated MTX uptake 8-fold, and in CEM cells 4-fold. With the reference hypomethylating agent 5-aza-2′-deoxycytidine similar values were obtained. RX-3117 also increased PCFT gene expression and PCFT protein. (4) Conclusion: RX-3117 down-regulates DNMT1, leading to hypomethylation of DNA. From the increased protein expression of tumor-suppressor genes and functional activation of PCFT, we concluded that RX-3117 might have induced hypomethylation of the promotor.

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