Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To further investigate the role of p53 gene inactivation in gastric tumorigenesis, the mutational status of the p53 gene in primary human gastric cancer samples was examined. Reverse transcriptase polymerase chain reaction and subsequent direct sequencing of the p53 gene from gastric cancer samples revealed frequent point mutations of the p53 gene: some of these coincided with those previously identified in gastric cancer cell lines. In addition, both allelic deletion analysis using pYNZ 22 and polymerase chain reaction-restriction fragment length polymorphism analysis demonstrated an allelic deletion of the p53 gene in cancer tissue which contained a point mutation of the p53 gene in the remaining allele. Transfection of the wild-type or mutant p53 genes into gastric cancer cells showed that the wild-type but none of the mutated p53 genes suppressed the colony formation of gastric cancer cells. Furthermore, the incorporation of thymidine into DNA was reduced in cancer cells expressing the wild-type p53 gene. The glutathione S-transferase-wild type p53 fusion protein bound to simian virus 40 large T antigen in COS-1 cell lysate. None of the p53 fusion proteins containing mutations at codons 143, 175, 248, or 273 bound to simian virus 40 large T antigen. By contrast, two different mutant p53 fusion proteins containing mutations specifically observed in gastric cancer bound to simian virus 40 large T antigen. These results indicate that inactivation of the p53 gene through mutations and the allelic deletion may play an important role in gastric tumorigenesis. These mutations may cause a conformational change in the p53 protein resulting in the loss of the suppression by p53 of the growth of gastric cells, partly through disruption of the association of p53 protein with a cellular component.
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PMID:p53 gene mutations in human gastric cancer: wild-type p53 but not mutant p53 suppresses growth of human gastric cancer cells. 132 85

To determine the expression of multidrug resistance-associated protein (MRP) gene and its role in gastric and colon cancers, we analyzed 10 gastric and 10 colon non-drug-selected cell lines and a similar number of tissue samples of these cancers. We compared the expression of MRP and mdrl mRNA in cell lines and tissues using reverse-transcriptase polymerase chain reaction. In mdrl-negative cells, the relationship between the level of MRP gene expression and sensitivity to anticancer drugs was examined. The effect of verapamil, an MRP-modulating agent, was also examined in these cells. The expression of MRP gene in gastric cancer cell lines varied from a low to a high level, but mdrl was not detected in any of these cell lines. Colon cancer cell lines expressed low to intermediate levels of MRP gene, and half of the cells co-expressed low to high levels of mdrl. In tissue samples, the expression pattern of the two multidrug resistance (MDR) genes was broadly similar to that described for the cell lines, except that most of the gastric cancer tissue samples did express low levels of mdrl. No significant correlation was observed between the level of MRP gene expression and sensitivity to anticancer drugs in gastric and colon cell lines. However, verapamil significantly increased the sensitivity to etoposide, doxorubicin and vincristine in cells highly expressing MRP gene. Our results indicate that MRP gene may be important in conferring MDR in gastric and colon cancer cells.
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PMID:The multidrug resistance-associated protein gene confers drug resistance in human gastric and colon cancers. 904 62

The effects of the macromolecular synthesis inhibitors 5,6-dichloro-1-beta-D-ribofuranosyl benzimidazole (DRB), actinomycin D, and cycloheximide on the human gastric cancer TMK-1 cell line were studied. These agents inhibited DNA, RNA, or protein synthesis efficiently and induced cell death rapidly in a wide range of concentrations. After 8 hr of exposure to these agents, the cells exhibited morphological features of apoptosis, including cell shrinkage, nuclear condensation, DNA fragmentation, and formation of apoptotic bodies. Western blot analysis revealed that these inhibitors altered the protein levels of apoptosis-related gene products such as c-Myc, Bcl-X(S), and the mutant p53 (mp53) in TMK-1 cells markedly. The c-myc mRNA and protein levels were decreased initially and were then induced markedly to a new level after 4 hr of exposure to DRB, a RNA polymerase II inhibitor. The Bcl-X(S) levels were increased rapidly after treatment with all of these agents, whereas the levels of Bcl-X(L) and Bax remained largely unchanged. Northern blot analysis indicated that the c-myc overexpression is concomitant to DRB-induced DNA fragmentation and that the increased mp53 protein level was mainly a posttranscriptional event. Our observations suggest that the up-regulation of Bcl-X(S) may serve as an important mechanism for the apoptosis triggered by these inhibitors. This study also provides evidence for the notion that interference with the cellular survival pathway may lead to apoptosis.
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PMID:Effects of transcription and translation inhibitors on a human gastric carcinoma cell line. Potential role of Bcl-X(S) in apoptosis triggered by these inhibitors. 917 10

Reverse transcriptase-polymerase chain reaction (RT-PCR) targeted at keratin 19 mRNA was applied to detect circulating cancer cells in the peripheral and portal blood of pancreatic and gastric cancer patients. Keratin 19 mRNA expression was studied by RT-PCR in cancer tissues (12 pancreatic and 15 gastric cancers) and in peripheral and/or portal blood samples from patients with pancreatic cancer (stage I, n = 5; stage II, n = 1; stage III, n = 15; stage IV, n = 19), gastric cancer (stage la,b, n = 28; stage II, n = 9; stage IIIa,b, n = 5; stage IVa,b, n = 7) and benign pancreatic diseases (n = 7). Peripheral blood samples from 50 healthy volunteers served as controls. RT-PCR was conducted in duplicate in each sample, and only samples showing keratin 19 transcript in both determinations were considered as being positive. All the pancreatic and gastric cancers, but none of the control blood samples, were found to be positive. Dilution study using pancreatic cancer cells serially mixed against peripheral blood showed that detection sensitivity was more than one cancer cell in 10(6) peripheral blood mononuclear cells. In pancreatic cancer patients, RT-PCR analysis of the portal blood samples gave positive results in one stage III and one stage IV patient, and that of peripheral blood samples gave positive results in 2 stage IV patients. No positive results were obtained in any of the blood samples from gastric cancer patients. Our results indicate that incidence of circulating cancer cells is unexpectedly very low even in advanced pancreatic and gastric cancer patients.
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PMID:Detection of pancreatic and gastric cancer cells in peripheral and portal blood by amplification of keratin 19 mRNA with reverse transcriptase-polymerase chain reaction. 924 82

We examined the expression of FGF-2 mRNA in 16 early and 14 advanced gastric cancer by in situ hybridisation to elucidate its role in cancer progression. Anti-sense RNA probes were synthesized by transcribing the subcloned vector with T7 RNA polymerase in the presence of digoxigenin-labeled UTP. FGF-2 mRNA was located mainly in the cytoplasm around the nuclei of endothelial cells, fibroblasts and carcinoma cells. The expression was more frequently in the diffuse type carcinomas (4/7, 57%) than in the intestinal type tumours (5/23, 22%). The survival rates of advanced gastric cancers with FGF-2 mRNA expression were significantly lower than those without FGF-2 mRNA expression (p < 0.01). No significant correlation was seen with other clinicopathological factors. These results suggest that FGF-2 may play an important role for the growth of diffuse type gastric cancers, particularly at their advanced stage.
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PMID:Expression of fibroblast growth factor 2 mRNA in early and advanced gastric cancer. 949 85

Expression of mRNA for heregulin (HRG), a member of the epidermal growth factor (EGF) family and its receptors, ErbB-3 and ErbB-4, were evaluated in human upper gastrointestinal (GI) mucosa. Multi-target reverse-transcriptase polymerase chain reaction (RT-PCR) analysis using capillary electrophoresis and laser-induced fluorescence allowed us to quantify the minute amounts of mRNA from one biopsy specimen with high sensitivity. HRG, ErbB-3 and ErbB-4 mRNA were detected in esophagus, stomach and duodenum and the highest expression was found in duodenum. In gastric cancer, mRNA for ErbB-4 was significantly overexpressed. Immunoreactivity of ErbB-4 in carcinoma cell membrane was also confirmed. These findings suggest that HRG and its receptors, ErbB-3 and ErbB-4 may be physiologically significant in the human upper GI mucosa, especially in duodenum, and that ErbB-4 may contribute to the growth of gastric cancer.
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PMID:Expression of mRNA for heregulin and its receptor, ErbB-3 and ErbB-4, in human upper gastrointestinal mucosa. 971 81

Retinoic acids, vitamin A-related compounds, are known to be inhibitors of telomerase. We found that fucoxanthin from the sea alga Petalonia bingamiae is a potent inhibitor of mammalian replicative DNA polymerases (i.e., pol alpha, delta and epsilon). Since fucoxanthin is a carotenoid (provitamin A-related) compound, we characterized the biochemical modes of vitamin A-related compounds including vitamin A and provitamin A in this report. Subsequently, we found that fucoxanthin, all-trans retinal (RAL, vitamin A aldehyde) and all-trans retinoic acid (RA, vitamin A acid) inhibited the activities of replicative DNA polymerases with IC(50) values of 18-190, 14-17 and 8-30 microM, respectively. On the other hand, all-trans retinol (vitamin A) did not influence any of the DNA polymerase activities. RA inhibited not only the activities of pol alpha, delta and epsilon with IC(50) values of 30, 28 and 8 microM, respectively, but of pol beta with an IC(50) value of 27 microM. The tested vitamin A-related compounds did not influence the activities of DNA polymerases from a higher plant, cauliflower, prokaryotic DNA polymerases, or DNA metabolic enzymes such as human immunodeficiency virus type 1 reverse transcriptase, T7 RNA polymerase and bovine deoxyribonuclease I. RAL and RA should be called selective inhibitors of mammalian DNA polymerases including telomerase, and RAL was a specific inhibitor of mammalian replicative DNA polymerases. As expected from these results in vitro, some of them could prevent the growth of NUGC-3 human gastric cancer cells, and especially RAL was a potent antineoplastic agent with an LD(50) value of 19 microM. The cells were halted at G1 phase in the cell cycle by RAL.
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PMID:Vitamin A-related compounds, all-trans retinal and retinoic acids, selectively inhibit activities of mammalian replicative DNA polymerases. 1195 16

The effects of extensive intraoperative peritoneal lavage (EIPL) for gastric cancer patients with peritoneal free cancer cells were investigated. This study was based on 22 consecutive patients with peritoneal free cancer cells, among 663 patients who underwent curative surgical treatment for advanced gastric cancer. The 22 patients were followed up for 2 years or until death. These patients were divided into three groups: group 1, patients with no additional intraoperative therapy (from 1989 to 1992; n = 8); group 2, patients with intraoperative intraperitoneal chemotherapy alone (from 1992 to 1995; n = 7); and group 3, patients with EIPL followed by intraoperative intraperitoneal chemotherapy (from 1996 to 1999; n = 7). Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed that viable cancer cells were not detected after the eighth EIPL in a gastric cancer patient with numerous intraperitoneal free cancer cells. In group 3, 4 of the 7 patients survived for more than 2 years, including 3 with cancer-free status, whereas no patient survived cancer-free in groups 1 and 2. The peritoneal recurrence rates and cancer-specific 2-year survival rates in groups 1, 2, and 3 were 100%, 85.7% and 42.9%; and 0%, 14.3%, and 57.1%, respectively. The 2-year survival rate of group 3 was significantly higher than that of group 1 (P = 0.017) and that of group 2 (P = 0.025). In a subset analysis, patients with peritoneal free gastric cancer cells but no macroscopic dissemination showed a statistically significant improvement in survival those treated with EIPL compared with those not treated with EIPL.
Gastric Cancer 2002
PMID:Extensive intraoperative peritoneal lavage and chemotherapy for gastric cancer patients with peritoneal free cancer cells. 1237 44

Advanced gastric cancer is often accompanied by metastasis to the peritoneum, resulting in a high mortality rate. Mechanisms involved in gastric cancer metastasis have not been fully clarified because metastasis involves multiple steps and requires a combination of altered expressions of many different genes. Thus, independent analysis of any single gene would be insufficient to understand all of the aspects of gastric cancer peritoneal dissemination. In this study, we performed a global analysis of the differential gene expression of a gastric cancer cell line established from a primary main tumour (SNU-1) and of other cell lines established from the metastasis to the peritoneal cavity (SNU-5, SNU-16, SNU-620, KATO-III and GT3TKB). The application of a high-density cDNA microarray method made it possible to analyse the expression of approximately 21 168 genes. Our examinations of SNU-5, SNU-16, SNU-620, KATO-III and GT3TKB showed that 24 genes were up-regulated and 17 genes down-regulated besides expression sequence tags. The analysis revealed the following altered expression such as: (a) up-regulation of CD44 (cell adhesion), keratins 7, 8, and 14 (epitherial marker), aldehyde dehydrogenase (drug metabolism), CD9 and IP3 receptor type3 (signal transduction); (b) down-regulation of IL2 receptor gamma, IL4-Stat (immune response), p27 (cell cycle) and integrin beta4 (adhesion) in gastric cancer cells from malignant ascites. We then analysed eight gastric cancer cell lines with Northern blot and observed preferential up-regulation and down-regulation of these selected genes in cells prone to peritoneal dissemination. Reverse transcriptase-polymerase chain reaction confirmed that several genes selected by DNA microarray were also overexpressed in clinical samples of malignant ascites. It is therefore considered that these genes may be related to the peritoneal dissemination of gastric cancers. The results of this global gene expression analysis of gastric cancer cells with peritoneal dissemination, promise to provide a new insight into the study of human gastric cancer peritoneal dissemination.
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PMID:Differential gene expression profiles of gastric cancer cells established from primary tumour and malignant ascites. 1240 56

Quantitative and qualitative analyses of mRNAs from a small number of cells are extremely important for studies on gene expression in various physiological and pathological conditions in multicellular organisms. We present here an effective method for high-fidelity global mRNA amplification for in vivo gene expression profiling of as few as 100 cells obtained by laser-captured microdissection (LCM). This method, called TALPAT, is based on T7 RNA polymerase-mediated transcription, adaptor ligation, and PCR amplification followed by T7-transcription. More than 80% of genes were commonly identified as a more than 3-fold changed gene among three gastric cancer cell lines using cRNA amplified by both TALPAT and the ordinary in vitro T7-transcription. The reproducibility of TALPAT was validated by microarray analysis on 100 breast cancer cells obtained by LCM. For the application of the LCM-TALPAT method, we successfully obtained expression profiles of gastric cancer cells and the mesenchymal cells, enabling us to understand in vivo cell-to-cell cross-talk in the microenvironment.
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PMID:A faithful method for PCR-mediated global mRNA amplification and its integration into microarray analysis on laser-captured cells. 1255 60


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