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

---

Query: EC:1.2.1.13 (glyceraldehyde-3-phosphate dehydrogenase)
6,511 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To identify and characterize genes, the products of which play a role in pancreatic adenocarcinoma, we constructed a complementary DNA (cDNA) library using mRNA from the pancreatic adenocarcinoma cell line HPAF, grown as a nude mouse tumor. Through differential screening, we identified a cDNA clone, pII5B, that is homologous to an mRNA expressed at significantly higher levels in HPAF cells than in normal human pancreas. The pII5B cDNA was homologous to the 3'-untranslated region of glyceraldehyde-3-phosphate dehydrogenase (GAPDH, EC 1.2.1.12)mRNA. Partial sequencing of several HPAF tumor GAPDH cDNA clones revealed no significant differences from previously published GAPDH cDNA sequences. Increased levels of GAPDH mRNA, relative to actin mRNA levels, were found in six pancreatic adenocarcinoma cell lines and two nude mouse tumors, when compared to normal pancreas. Enolase and glucose transporter mRNA levels were also increased in HPAF cells and nude mouse tumor, suggesting a general increase in expression of genes associated with glycolysis in pancreatic adenocarcinoma. Levels of GAPDH protein were elevated in nude mouse tumors and fresh human pancreatic adenocarcinomas compared to normal pancreas. High GAPDH levels may be characteristic of human adenocarcinomas, since colon adenocarcinomas also exhibited high levels of GAPDH compared to normal colon.
...
PMID:Increased glyceraldehyde-3-phosphate dehydrogenase gene expression in human pancreatic adenocarcinoma. 318 54

Detection and quantitation of circulating cancer cells in peripheral blood may improve cancer staging and monitoring. This study explored the feasibility of using circulating cancer cell detection in peripheral blood for the rapid assessment of chemotherapeutic response. Cytokeratin 19 mRNA was amplified by nested reverse transcriptase-PCR in the peripheral blood of 29 healthy volunteers, 33 pneumonia patients, and 86 lung cancer patients. Circulating cancer cells in the peripheral blood were semiquantitatively determined by taking the ratio of cytokeratin 19 band intensity from the second round of nested PCR to the glyceraldehyde-3-phosphate dehydrogenase band intensity from the first round of PCR amplification. The detection limit of the method was 1 cancer cell in 107 peripheral blood mononuclear cells. The positive detection rate was 40% for lung adenocarcinoma patients of all stages, 41% for squamous carcinoma patients of all stages, and 27% for small cell lung cancer patients. Only one control sample from a pneumonia patient showed a positive result (1.6%). The quantitative method reliably and sensitively estimated cancer cell numbers in the peripheral blood of lung cancer patients. Serial measurement of the relative number of circulating cancer cells correlated with the tumor burden and treatment response of patients. This method may help rapidly assess the efficacy of anticancer treatment, redefine cancer staging, and facilitate the design of better therapeutic strategies for the treatment of cancer patients.
...
PMID:Detection and quantitation of circulating cancer cells in the peripheral blood of lung cancer patients. 966 88

S100A4 belongs to the S100 subfamily of calcium-binding proteins and has been suggested to be directly involved in invasion and metastasis of rodent and human tumour cells. The present study demonstrates that interferon gamma (IFN-gamma), but not IFN-alpha and IFN-beta, down-regulates the S100A4 mRNA level in colon adenocarcinoma WiDr cells in time- and dose-dependent manners. The effect was not associated with any cytotoxicity and was specific for the S100A4 mRNA, since the levels of the S100A6 and GAPDH mRNAs were not significantly affected by the treatment. IFN-gamma also strongly suppressed the S100A4 mRNA expression in HT-29 cells, but weakly in Colo201 cells. Flow cytometric analysis revealed that the level of the IFN-gamma receptor expression in Colo201 cells was lower than that in WiDr and HT-29 cells, suggesting that the suppression of the S100A4 expression by IFN-gamma depends on the amount of cell surface IFN-gamma receptor protein. IFN-gamma had no effect on the transcription rate of the S100A4 gene but reduced the stability of the S100A4 mRNA. WiDr cells treated with IFN-gamma showed reduced motile ability, further supporting the assumption that the S100A4 gene product is involved in controlling cell motility.
...
PMID:Suppression of metastasis-associated S100A4 gene expression by gamma-interferon in human colon adenocarcinoma cells. 1038 88

Colon cancer incidence and mortality rates are lower in females compared with males, and numerous epidemiological studies suggest that estrogen replacement therapy (ERT) reduces cancer risk in postmenopausal women. Two estrogen receptor (ER) subtypes, ERalpha and ERbeta, mediate genomic effects in target cells. The aim of this study was to determine the relative mRNA expression levels for ER subtypes and ERbeta isoforms in colon tumors, normal colonic mucosa, and colon cancer cell lines. ERalpha and ERbeta isoform mRNA levels were investigated in paired samples of colon tumors and normal mucosa from 26 patients using comparative reverse transcription-PCR and then Southern analyses. Constitutive steroid hormone receptor mRNA levels were determined for five colon adenocarcinoma cell lines using reverse transcription-PCR, and ERbeta levels were further studied in Caco-2 cells using Northern and Western analyses. ERbeta mRNA steady-state levels (relative to glyceraldehyde-3-phosphate dehydrogenase mRNA) were significantly decreased in colon tumors compared with normal mucosa in female patients. ERbeta1 and ERbeta2 isoform mRNA levels were significantly decreased in tumors from female patients, and ERbeta1 mRNA levels were also significantly lower in tumors from female patients compared with tumors from males. ERalpha mRNA levels were much lower than ERbeta levels and were similar between normal mucosa and tumor samples in both genders. ERbeta mRNA was detected in Caco-2, T84, and SW1116 cell lines and all lines were essentially negative for ERalpha mRNA. Caco-2 cells coexpressed ERbeta1, ERbeta2, and ERbeta5 mRNA, though a single protein transcript was observed. ERbeta protein was detected in normal colonic superficial epithelium, vascular smooth muscle and endothelium, and enteric neurons by immunohistochemistry. These data show that ERbeta is the predominant ER subtype in the human colon and that decreased levels of ERbeta1 and ERbeta2 mRNA are associated with colonic tumorigenesis in females. This information suggests that activation of ERbeta-mediated processes in the superficial colonic epithelium may have a role in the preventive effects observed for female gender and ERT usage.
...
PMID:Expression of estrogen receptor (ER) subtypes and ERbeta isoforms in colon cancer. 1121 61

We screened samples of tumour and peripheral normal tissue for differential expression of oncogenes by using an approach of detecting the differences in expression of a number of oncogenes simultaneously. Total RNA was isolated from 29 pairs of normal and tumour tissue samples from patients with gastric adenocarcinoma. Seven pairs of primers for oncogenes most probably associated with the process of carcinogenesis in stomach including cyclin E, c-erbB-3, HGR, c-met, TDGF/cripto, FGF-4, and EGF were used for the construction of fluorescent multiplex RT-PCR. Sense primers were 5' end-labelled with a fluorescent dye. 5-7 gastric oncogenes were simultaneously analysed for overexpression. Multiplex reverse transcription with a set of unlabeled primers was followed by a PCR reaction by adding the corresponding set of fluorescent labelled PCR-primers. Expression of oncogenes was compared to GAPDH internal standard. Multiplex fluorescent RT-PCR results were analysed by capillary electrophoresis on ABI-PRISM 310 Genetic Analyzer. Differential expression of oncogene mRNAs in tumour and normal tissue was assessed by comparison of oncogene/GAPDH ratios in tumours and their peripheral normal mucosa. Our results show, that in most patients, comparing to normal tissue, we could estimate overexpression of at least one oncogene in a sample.
...
PMID:Assessment of differential expression of oncogenes in gastric adenocarcinoma by fluorescent multiplex RT-PCR assay. 1167 35

The expression levels of mRNAs for MDR1 (P-glycoprotein), multidrug resistance-associated proteins (MRP1, MRP2), and cytochrome P450 3A (CYP3A) in Caco-2 cells were quantitatively compared with those in human duodenal enterocytes, normal colorectal tissues, and colorectal adenocarcinomas. Caco-2 cells (passages 36-88) were kindly supplied by several laboratories in Japan. Human duodenal enterocytes were obtained from five healthy male volunteers. Normal colorectal tissues and colorectal adenocarcinomas were simultaneously obtained from seven patients with primary colorectal adenocarcinoma. MDR1, MRP1, MRP2, and CYP3A mRNA levels were determined by real-time quantitative polymerase chain reactions (PCR). Relative concentrations of mRNAs for target proteins (MDR1, MRP1, MRP2, and CYP3A) and glyceraldehyde-3-phosphate dehydrogenase in Caco-2 cells were 1.00 +/- 0.15, 1.02 +/- 0.06, 0.94 +/- 0.10, and 0.68 +/-0.60, respectively, and those in human enterocytes were about 12-, 3-, 7-, and 8000-fold higher than in the Caco-2 cells, respectively. In contrast, MDR1, MRP1, and CYP3A mRNA levels in Caco-2 cells were comparable to those in normal colorectal tissue and colorectal adenocarcinoma.
...
PMID:Real-time quantitative polymerase chain reaction for MDR1, MRP1, MRP2, and CYP3A-mRNA levels in Caco-2 cell lines, human duodenal enterocytes, normal colorectal tissues, and colorectal adenocarcinomas. 1174 4

In order to identify genes associated with metastasis of ductal pancreatic adenocarcinoma we investigated pancreatic tumor cell lines derived from an orthotopic pancreatic tumor model in SCID mice. Transcriptional profiling (Affymetrix Gene Chip Technology) was performed with cell lines derived from the primary tumor and metastatic lesions such as mesentery, liver and lungs. We scored for genes commonly deregulated in the cell lines derived from the metastatic lesions. Of 7070 genes investigated, 59 (0.83%) were found to be deregulated in the cell lines derived from the metastatic lesions. We grouped these genes into different categories such as transcription, translation, cytoskeleton, cell adhesion, chromosome instability, tumor suppressor genes, enzymes and "others". The most remarkable features of the system are the up-regulation of high mobility group protein HMG-I (Y), twenty-one ribosomal proteins, GAPDH and the laminin receptor in the cell lines derived from the metastatic lesions, whereas tumor suppressor genes such as maspin and RB1 were down-regulated. Inhibition or reconstitution of the activity of these targets are an emerging strategy for inhibition of metastasis in this system.
...
PMID:Transcriptional profiling of cell lines derived from an orthotopic pancreatic tumor model reveals metastasis-associated genes. 1184 76

C/EBP delta, a member of the leucine zipper transcription factor family, is expressed at higher levels in the lung than in any other tissue. We detected C/EBP delta mRNA and protein in NCI-H441 cells, a cell line derived from a human adenocarcinoma that produces surfactant protein A (SP-A). NCI-H441 cells were exposed to phosphorothioate-substituted antisense oligonucleotides directed against C/EBP delta. After exposure to the oligonucleotides, cells were harvested, total RNA prepared, and levels of mRNA for C/EBP delta, SP-A and a control, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), were quantified from Northern blots. An oligonucleotide that overlapped the translational start was effective in reducing C/EBP delta mRNA. Oligonucleotides that corresponded to regions upstream and downstream from the translational start were not as effective. The loss of C/EBP delta was accompanied by a decrease in the level of SP-A mRNA. The overlapping oligonucleotide was tested more extensively. After 72 h, antisense oligonucleotide at 3 and 5 microM reduced the level of C/EBP delta mRNA and protein by 50% or more as compared with sense and scrambled controls. The SP-A mRNA level was reduced even more, by about 75%. GAPDH mRNA was not affected. We conclude that C/EBP delta plays a role in the regulation of SP-A gene expression.
...
PMID:A role for C/EBP delta in human surfactant protein A (SP-A) gene expression. 1202 Aug 23

Ceramide has been demonstrated as one of the upstream regulators of telomerase activity. However, the role for ceramide in the control of telomere length remains unknown. It is shown here that treatment of the A549 human lung adenocarcinoma cells with C(6)-ceramide results in rapid shortening of telomere length. During the examination of ceramide-regulated telomere-binding proteins, nuclear glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was identified to associate with both single- and double-stranded telomeric DNA with high specificity in vitro. The association of nuclear GAPDH with telomeres in interphase nuclei was also demonstrated by co-fluorescence in situ hybridization and chromatin immunoprecipitation analysis. Further data demonstrated that the nuclear localization of GAPDH is regulated by ceramide in a cell cycle-dependent manner parallel with the inhibition of its telomere binding activity in response to ceramide. In addition, the results revealed that nuclear GAPDH is distinct from its cytoplasmic isoform and that telomere binding function of nuclear GAPDH is strikingly higher than the cytoplasmic isoform. More importantly, the functional role for nuclear GAPDH in the maintenance and/or protection of telomeric DNA was identified by partial inhibition of the expression of GAPDH using small interfering RNA, which resulted in rapid shortening of telomeres. In contrast, overexpression of nuclear GAPDH resulted in the protection of telomeric DNA in response to exogenous ceramide as well as in response to anticancer drugs, which have been shown to induce endogenous ceramide levels. Therefore, these results demonstrate a novel function for nuclear GAPDH in the maintenance and/or protection of telomeres and also show that mechanisms of the rapid degradation of telomeres in response to ceramide involve the inhibition of the telomere binding activity of nuclear GAPDH.
...
PMID:Rapid shortening of telomere length in response to ceramide involves the inhibition of telomere binding activity of nuclear glyceraldehyde-3-phosphate dehydrogenase. 1463 Sep 8

Colorectal-carcinoma specimens are heterogeneous and include areas of nonmalignant mucosal and connective tissue. For those study designs in which laser microdissection and RNA preamplification are impracticable, the optimal yield of genuine cancer RNA is a key factor in gene-expression analysis. In this study we compared alternative methods of tissue purification. Three contiguous 0.5-cm(3) samples taken from an advanced primary adenocarcinoma of the sigmoid colon were processed immediately after surgery with the use of the following methods: (1) cryotomy after manual dissection (CMD), (2) microscopically assisted manual dissection (MAMD), and (3) tumor-cell isolation with the use of Ber-EP4 antibodies and Dynabeads (Dynal Biotech GmbH, Hamburg, Germany; technique abbreviated as DB). We generated gene-expression profiles with the use of GeneChip technology (Affymetrix, Santa Clara, Calif) and recorded preparation times, costs, and RNA quantity and quality. CMD took 60 minutes, MAMD 180 minutes, and DB 90 minutes to isolate 22, 8, and 23 microg of RNA, respectively. Expenses for materials amounted to 41, 23, and 91 US dollars for CMD, MAMD, and DB, respectively. The 3'/5' ratio, as determined with the GeneChips, for GAPDH/beta-actin was 1.01:1.03 for CMD, 1.13:1.28 for MAMD, 1.43:1.68 for DB, K-ras, APC, smad 2, transforming growth factor-beta, and p53 were marked as present in all cases, with the exception of APC, which was graded as marginal on DB. The correlation values of gene-expression profiles were 91% (CMD/DB), 93% (CMD/MAMD), and 97% (DB/MAMD). All 3 methods provided enough RNA, of sufficient quality, for gene-expression microarray analysis in colorectal carcinoma. Cross-methodologic analyses of array data should not be performed uncritically.
...
PMID:Tissue preparation for gene expression profiling of colorectal carcinoma: three alternatives to laser microdissection with preamplification. 1519 50


1 2 3 4 Next >>

---