Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that fibroblast growth factor receptor 2 (FGFR2) plays an important role in gastric carcinogenesis. In this study, we assessed DNA methylation status in the promoter region of FGFR2 gene in gastric cancer cell lines, and indicated that this region was highly methylated, compared with FGFR2-expressing gastric cancer cell lines. Moreover, the restoration of FGFR2 expression by treating methylated cells with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine strongly suggests that the loss of FGFR2 expression may be due to the aberrant hypermethylation in the promoter region of the FGFR2 gene. Thus, our results suggest that the epigenetic silencing of FGFR2 through DNA methylation in gastric cancer may contribute to tumor progression.
 ...
PMID:Aberrant hypermethylation of the FGFR2 gene in human gastric cancer cell lines. 1745 42

DNA methylation is crucial for normal development, but gene expression altered by DNA hypermethylation is often associated with human diseases, especially cancers. The gene TSPYL5, encoding testis-specific Y-like protein, was previously identified in microarray screens for genes induced by the inhibition of DNA methylation and histone deacetylation in glioma cell lines. The TSPYL5 showed a high frequency of DNA methylation-mediated silencing in both glioma cell lines and primary glial tumors. We now report that TSPYL5 is also inactivated by DNA methylation and could be a putative epigenetic target gene in gastric cancers. We found that the expression of TSPYL5 mRNA was frequently downregulated and inversely correlated with DNA methylation in seven out of nine gastric cancer cell lines. TSPYL5 mRNA expression was also restored after treating with a DNA methyltransferase inhibitor. In primary gastric tumors, methylation-specific PCR results in 23 of the 36 (63.9%) cases revealed that the hypermethylation at CpG islands of the TSPYL5 was detectable at a high frequency. Furthermore, TSPYL5 suppressed the growth of gastric cancer cells as demonstrated by a colony formation assay. Thus, strong associations between TSPYL5 expression and hypermethylation were observed, and aberrant methylation at a CpG island of TSPYL5 may play an important role in development of gastric cancers.
 ...
PMID:Gene silencing of TSPYL5 mediated by aberrant promoter methylation in gastric cancers. 1805 62

This study investigates the varied expression of DNA methyltransferase (DNMT) proteins in gastric cancer (GC) and their relationship with the biological behavior of the tissues. Immunohistochemistry was used to detect the expression of the 3 DNMTs in gastric tissues. We discovered that the positive rates of DNMT1, DNMT3a, and DNMT3b expression in GC tissues were 81.6%, 81.6%, and 68.4%, respectively, and they were significantly higher than those of both para-cancerous (39.5%, 50%, and 44.7%) and normal tissues (10.5%, 10.5%, and 7.9%). DNMT1 was well distributed in the cytoplasm and nuclei of tumor cells or glands, while DNMT3a and 3b were well distributed only in the cytoplasm, as shown by staining a dark brown color. A significant correlation between the DNMT1 and DNMT3a proteins (P < 0.01), a low correlation between DNMT3a and DNMT3b (P < 0.05), and no correlation between DNMT1 and DNMT3b (P > 0.05) were observed. DNMT1 protein expression exhibited no correlation with age, lymphnode metastasis, and also tumor differentiation, but it may have had a correlation with gender. The DNMT3 family was not associated with these factors. Therefore, DNMT overexpression is involved in gastric tumorigenesis, but there is no correlation between the DNMTs and the biological behaviors of tissues.
 ...
PMID:The expression and clinical significance of DNA methyltransferase proteins in human gastric cancer. 1825 30

The National Comprehensive Cancer Network guidelines recommend radiotherapy as a standard treatment for patients with a high risk of recurrence in gastric cancer. Because radiation is harmful to the surrounding organs, a radiation sensitizer might therefore be useful to decrease the side effects of patients with advanced gastric carcinoma. The aim of the current study was to clarify the effect of a DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (CdR), on radiation sensitivity in gastric cancer cells. Five gastric cancer cell lines, OCUM-2M, OCUM-12, KATO-III, MKN-45, and MKN-74, were used. The effects of 5-aza-CdR with irradiation on the growth activity, cell-cycle distribution, apoptosis, and apoptosis-associated gene expression were examined. 5-aza-CdR sensitized three of five gastric cancer cell lines to radiation. A combination of irradiation and 5-aza-CdR significantly (P<0.05) decreased the growth activity compared with irradiation alone in OCUM-2M, OCUM-12, and MKN-45 cells, but not in KATO-III and MKN-74 cells. The percentage of cells in G2-M phase and the apoptotic rate with irradiation in combination with 5-aza-CdR were increased in OCUM-2M, OCUM-12, and MKN-45 cells compared with irradiation alone, but not in KATO-III and MKN-74 cells. 5-aza-CdR increased the expression of p53, RASSF1, and death-associated protein kinases (DAPK) genes compared with the control or irradiation alone. These findings suggest that 5-aza-CdR might therefore be useful as a radiation sensitizer to treat some types of gastric carcinoma. The arrest at G2-M phase and increased apoptotic rate might be partly mediated by enhanced expression of the p53, RASSF1, or DAPK gene families by 5-aza-CdR.
 ...
PMID:DNA methyltransferase inhibitor 5-aza-CdR enhances the radiosensitivity of gastric cancer cells. 1903 91

Sporadic gastric cancer is considered to be the result of a progressive accumulation of genotypic changes due to an adverse environment (i.e., diet and Helicobacter pylori infection). The main molecular mechanism implicated in cancer-related molecular alterations is of epigenetic nature, which includes DNA methylation and histone modification. Diet may influence the methylation status supplying methyl groups S-adenosyl-methionine formation, modifying DNA methyltransferase activity and influencing DNA demethylation activity. H. pylori may affect DNA methyltransferase directly or through inflammatory mediators (e.g., reactive oxygen species or nitric oxide). In conclusion, gastric cancer is a multistep process due to an adverse environment over a long period of time. Dietary habit and H. pylori infection can induce epigenetic alterations that, in turn, trigger gastric carcinogenesis.
 ...
PMID:Epigenetic alterations due to diet and Helicobacter pylori infection in gastric carcinogenesis. 1907 59

Detoxification mechanisms can play a pivotal role in determining tumor cell responses to platinum-based chemotherapy. Glutathione S-transferase-pi (GSTP1) belongs to a supergene family of detoxifying enzymes involved in the prevention of DNA damage and subsequent platinum resistance in numerous cancers. The role of GSTP1 in gastric cancer sensitivity to chemotherapy is, however, not known. In this study, we found that the human gastric cancer cell line MGC803 was significantly more sensitive to cis-platinum (CDDP) than the other gastric cancer lines examined (BGC823 and SGC7901). To explore the potential role of GSTP1 in drug resistance, we measured GSTP1 expression in these cells. GSTP1 mRNA and protein were not detectable in MGC803 cells; both were present in BGC823 and SGC7901 cells. GSTP1 CpG island DNA methylation was examined. We report that promoter hypermethylation was associated with the absence of GSTP1 expression in MGC803 cells. Treatment of these cells with 5-aza-2'-deoxycytidine, a DNA methyltransferase inhibitor, restored GSTP1 expression and suppressed sensitivity to CDDP. The selective mitogen-activated protein kinase/extracellular regulated kinase (ERK) pathway inhibitor PD98059 decreased GSTP1 expression in 5-aza-2'-deoxycytidine-treated cells. A similar decrease was observed in the BGC823 and SGC7901 cell lines, suggesting that mitogen-activated protein kinase/ERK signaling stimulates GSTP1 expression. CDDP sensitivity was also enhanced by PD98059. These observations indicate that somatic promoter hypermethylation and impaired ERK signaling are associated with decreased GSTP1 expression and CDDP sensitivity in gastric cancer cell lines. Evaluation of promoter methylation and ERK activity may be useful for predicting tumor sensitivity to platinum-based chemotherapeutics.
 ...
PMID:GSTP1 determines cis-platinum cytotoxicity in gastric adenocarcinoma MGC803 cells: regulation by promoter methylation and extracellular regulated kinase signaling. 1939 19

To investigate the association of single-nucleotide polymorphism (SNP) in DNA methyltransferase 3B (DNMT3B) gene and the risk of gastric cancer (GC), we detected -149C>T and -579G>T in the promoter region of the DNMT3B gene by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing analysis. The DNMT3B genotype was determined in 259 gastric cancer patients and 262 healthy controls that were frequency matched for age and gender. Results showed that individuals with at least one -579G allele were also at significantly decreased risk of gastric cancer [odds ratio (OR), 0.43; 95% confidence interval (CI) 0.26-0.72] compared with those having a -579TT genotype. The -149C>T genotype distribution was irrelevant to the risk of gastric cancer (OR, 1.49; 95% CI, 0.17-17.94) in the studied Chinese population. In addition, data suggested that DNMT3B genetic polymorphism varied among different races, ethnic groups, and geographic areas.
 ...
PMID:DNMT3B promoter polymorphism and risk of gastric cancer. 1951 37

ERas is a recently identified oncogene that supports the tumorigenic growth of embryonic stem cells, it is constitutively active in the absence of mutation. ERas oncogene is expressed only in viviparity phase cells, but not in somatic cells because of epigenetic transcriptional silencing in the somatic phase. The aim of this study was to clarify the ERas expression and its epigenetic regulation in gastric cancer of somatic phase. Fifteen gastric cancer cell lines were used. ERas mRNA expression and its epigenetic regulation were examined by reverse transcription-polymerase chain reaction and bisulfite sequencing analysis. To identify a subset of cancer stem cells, termed 'side population' (SP) cells, flow cytometry analysis was performed. ERas is expressed in 8 of the 15 gastric cancer cell lines, but is silenced in the remaining 7 cancer cell lines and normal cell lines. Six of 7 cancer cell lines without ERas expression had promoter methylation, which correlated with silencing of ERas expression. ERas expression is re-activated following treatment with the DNA methyltransferase inhibitor 5-aza-CdR. The percentage of SP fraction of ERas-positive gastric cancer cells was significantly (p=0.024) higher (3.4+/-1.8%), in comparison to that of ERas-negative cells (1.6+/-0.4%). These findings suggested that the activating ERas oncogene might be associated with tumorigenic growth of somatic cells, and might be a putative molecule responsible for cancer stem cell-like characteristics in gastric cancer. Loss of methylation in the promoter of ERas might be one of mechanisms responsible for the re-expression of an embryonic oncogene in gastric cancer.
 ...
PMID:Epigenetic regulation of the embryonic oncogene ERas in gastric cancer cells. 1978 53

Down-regulated expression of human leukocyte antigen (HLA) class I molecules in many human cancers facilitate tumor cells to escape from immune attack. Promoter hypermethylation, one of the major epigenetic changes responsible for gene inactivation, plays an important role in gastric carcinogenesis. This study evaluated the expression and alteration of HLA class I molecules in a panel of 47 pairs of gastric cancer specimens with their noncancerous parts from Chinese patients by using immunohistochemistry (IHC), reverse transcription polymerase chain reaction (RT-PCR) and methylation-specific PCR (MSP) analysis. The expression of HLA-A, HLA-B/C and HLA class I complex was lost or down-regulated in human gastric cancer. The percentage of promoter methylation was 59.57% for HLA-A gene, 55.32% for HLA-B gene and 48.94% for HLA-C gene in gastric cancer, while it was decreased to 19.15%, 12.77% and 6.38% in the adjacent nontumor tissues, respectively. Seven of 10 (70%), 4 of 6 (66.7%) and 3 of 4 (75%) gastric cancer specimens with promoter hypermethylation at HLA-A, -B and -C loci showed transcriptional inactivation of HLA-A,-B and -C genes, suggesting an association between promoter hypermethylation and down-regulated expression of HLA class I molecules. Human gastric cancer cell line BGC-823 showed HLA-A down-regulation with promoter methylation of HLA-A locus. Treatment with DNA methyltransferase inhibitor restored the expression of HLA-A mRNA and surface HLA-A complex. Thus, our results showed that promoter hypermethylation might be one of the mechanisms that lead to HLA class I antigen down-regulation in gastric cancer.
 ...
PMID:Hypermethylation of HLA class I gene is associated with HLA class I down-regulation in human gastric cancer. 1988 94

The aim of this study was to detect the expression pattern of DNA methyltransferase 3B (DNMT3B) variants in primary gastric cancer (GC) and to explore the clinical significance of DNMT3B variants in gastric carcinogenesis. Specific polymerase chain reaction (PCR) primer sets were designed to distinguish individual DNMT3B variants according to their splicing patterns. Expression levels of DNMT3B variants were assessed by quantitative real-time RT-PCR in gastric cancer tissue, normal gastric mucosae and GC cell lines. The relationship between the expression patterns of the DNMT3B variants and corresponding clinical information was analyzed by observing the expression levels of different variants in the tumors. These results demonstrate that DNMT3B overexpression is related to late phase invasion (P=0.029) and intestinal type (P=0.012) in GC. DNMT3B3 expression was higher in normal tissue, compared to tumor tissue (P=0.033). In contrast, only 18, 32 and 35% of the patient tumors overexpressed DNMT3B1, DNMT3B4 and DNMT3B5, respectively. While taking into account environmental factors (H. pylori, Epstein-Barr virus infection), H. pylori infection elevated DNMT3B1 and DNMT3B3 variants in tumors, while increasing DNMT3B4 in both tumor and non-cancerous tissues. Our findings indicated that the expression of DNMT3B3 is the major splice variant in normal gastric mucosae and may be affected by H. pylori infection. Elevated DNMT3B variants may influence the progression of gastric cancer and may possibly be a powerful indicator for the disease.
 ...
PMID:Expression pattern and clinical significance of DNA methyltransferase 3B variants in gastric carcinoma. 2012 25


<< Previous 1 2 3 4 5 6 Next >>