Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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.
Cancer Res 1988 Nov 15
PMID:Increased glyceraldehyde-3-phosphate dehydrogenase gene expression in human pancreatic adenocarcinoma. 318 54

We have shown that a Mr 37,000 protein whose expression is strongly enhanced in human lung cancer tissues is the subunit of glyceraldehyde-3-phosphate (GAPDH, EC 1.2.1.12). We have isolated a GAPDH complementary DNA from human lung cancer cells and deduced the complete amino acid sequence of the encoded protein. The structure of the lung cancer GAPDH is identical to that of liver GAPDH. In addition, we have found that GAPDH mRNA expression is markedly increased in human lung cancer tissues. These results disclose a molecular basis of increased glycolysis in cancer cells and reveal an important role of energy creating reaction in cancer cell growth.
Cancer Res 1987 Nov 01
PMID:Enhanced expression of a glyceraldehyde-3-phosphate dehydrogenase gene in human lung cancers. 366 68

The messenger RNAs for the angiogenic acidic and basic fibroblast growth factors are expressed at a significantly higher level in samples of human benign neoplastic and hyperplastic tissue than in samples from breast cancers. However, approximately one in four malignant breast cancer samples contain basic fibroblast growth factor mRNA at the same level as in the benign lesions when basic fibroblast growth factor mRNA levels are corrected with respect to levels of expression of glyceraldehyde-3-phosphate dehydrogenase mRNA. A similar proportion of human malignant breast cancer cell lines express a high level of basic fibroblast growth factor mRNA. The results suggest that some malignant breast cancers and their constitutive carcinoma cells express abundant levels of basic fibroblast growth factor mRNA. The resultant production of basic fibroblast growth factor by breast cancer cells within some tumours may contribute to their development.
Br J Cancer 1994 Apr
PMID:Comparative expression of fibroblast growth factor mRNAs in benign and malignant breast disease. 751 6

Measurement of P-glycoprotein and the gene that encodes it, mdr-1, is an important tool for assessing the impact of multidrug resistance in clinical cancer. We evaluated mdr-1 expression by a quantitative polymerase chain reaction (PCR) assay in 78 biopsy samples from 48 patients with refractory lymphoma enrolled on a trial of infusional chemotherapy (EPOCH) in which R-verapamil was added as an antagonist of P-glycoprotein in a subset of patients whose tumors were unresponsive to treatment. Expression of mdr-1 was detectable in all biopsies at the time of enrollment on study, and a fourfold or greater increase in mdr-1 expression was noted in 42% of patients at the time of treatment failure. Expression of mdr-1 was also detectable in biopsies from patients at the time of diagnosis of lymphoma. An endogenous control gene, beta 2-microglobulin, was quantitated for normalization of the mdr-1 values. The use of beta 2-microglobulin expression for normalization was validated in a subset of samples by comparing Northern blots detecting beta 2-microglobulin, beta actin, and GAPDH gene expression. Immunoblot analysis suggested that no major discrepancy was present between mRNA expression and protein level. Immunophenotyping of lymphomatous lymph nodes showed that infiltration of tumor cells ranged from 8% to 95% and of normal T cells from 1% to 83%. Expression of mdr-1 in normal T cells and monocytes was also shown to be low. The mdr-1 levels in patient samples were independent of T-cell contamination, suggesting that the presence of normal cells has at best a small impact on mdr-1 measurements. Expression of mdr-1 in lymphoma can be quantitated by PCR, and wide variations in expression can be observed. Increased expression in patients with refractory disease supports an important role for Pgp in drug resistance in lymphoma. These studies will aid in the design and interpretation of clinical trials in lymphoma.
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PMID:Expression of mdr-1 in refractory lymphoma: quantitation by polymerase chain reaction and validation of the assay. 763 59

Monocyte derived cytokines (monokines) are important mediators in inflammatory diseases and cancer. Control of monokine expression is also a major therapeutic target in autoimmune inflammation. Whole blood cultures permit examination of monokine expression under conditions which emulate the in-vivo environment whilst avoiding many of the artefacts associated with monocyte separation and culture. Here we describe a system for measuring interleukin-1 beta, interleukin-1 alpha, interleukin-6 and tumour necrosis factor-alpha mRNA in stimulated human whole blood ex-vivo, which can be applied to specimens from treated patients. Oligodeoxyribonucleotide probes are designed to allow standardisation of hybridisation and washing procedures. Washing and reprobing of membranes in appropriate sequence permits measurement of each monokine mRNA and mRNA for glyceraldehyde-3-phosphate dehydrogenase in only 7 ml of lipopolysaccharide-stimulated human blood. The method has been used successfully in studies of dexamethasone and methotrexate action on lipopolysaccharide stimulated IL-beta gene expression.
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PMID:A system for assessment of monokine gene expression using human whole blood. 764 69

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH, EC 1.2.1.12) activity and mRNA content is altered in the androgen-responsive human prostate carcinoma cell line LNCaP after exposure to the synthetic androgen R1881. Elevation in GAPDH activity is noted as early as 24 h after treatment with 1 nM R1881 and lasts at least 96 h. R1881 has no effect on the activity of GAPDH in androgen-independent DU145 cells. LNCaP GAPDH mRNA content is lowered by treatment with 1 nM R1881; the magnitude of reduction appears to depend on the length of exposure. The results present at least one means by which androgen-responsive tissues may develop alterations in GAPDH mRNA or activity, as is found in certain tumor tissues.
Cancer Res 1995 Oct 01
PMID:Alteration of glyceraldehyde-3-phosphate dehydrogenase activity and messenger RNA content by androgen in human prostate carcinoma cells. 767 Dec 26

Fifteen samples from 11 patients suffering from chronic lymphocytic leukaemia (CLL; 5 untreated, 6 chemotherapeutically treated) were analysed for their individual gene expression of the multidrug resistance (MDR) associated genes encoding mdr1/P-glycoprotein, mrp, and topoisomerase II alpha/beta-isoenzymes by a complementary DNA polymerase chain reaction (cDNA-PCR) approach. The expression of glyceraldehyde-3-phosphate dehydrogenase (gapdh) served as standard. Thereby, we generally found high mdr1- and mrp-, but low topoisomerase II alpha-mRNA levels. While mdr1 levels of the CLL samples were mostly found to be in the range of values measured in the T-lymphoblastoid, P-glycoprotein MDR cell line CCRF VCR 100, mrp levels were usually found to be 2-4-fold higher compared therewith. This might represent a multifactorial MDR in CLL. In contrast to the low or even absent topoisomerase II alpha gene expression, however, the expression of the topoisomerase II beta gene was generally high in the CLL lymphocytes exceeding the value observed in the cell line CCRF VCR 100 up to 5-fold. mdr1 gene expression correlated significantly with mrp gene expression in samples from patients having received chemotherapy (rs = 0.5833, P < 0.05, n = 10). In two patients the follow-up analysis revealed combined increases in mdr1- and mrp-gene expression levels in the course of the disease.
Cancer Lett 1994 Oct 28
PMID:High mdr1- and mrp-, but low topoisomerase II alpha-gene expression in B-cell chronic lymphocytic leukaemias. 795 50

Differential hybridization was used to detect repair defects in xeroderma pigmentosum (XP) that are not amenable to current analyses. cDNA libraries were constructed from cytoplasmic RNA of normal and XP fibroblast strains (complementation groups A and D) and analyzed for differential gene expression. More than 40,000 lambda gt10 cDNA clones were differentially screened with in vitro transcripts made from cDNA in the pBluescript vector. Six differential clones were detected in the libraries of the XP group A and D strains which caused stronger or weaker signals when probed with transcripts from XP strains than with those from the normal strains. Two clones coded for mitochondrial genes: mitochondrial 16 S rRNA and ATPase 6L. Overexpression of mitochondrial genes in XP may indicate that functions of the ATP-generating system are impaired since such functions are intensified whenever they become insufficient, for example as a consequence of DNA damage. It is tempting to assume that abnormal mitochondria are one of the causes for the neurological malfunctions in XP. Furthermore, densitometric analysis of Northern blots revealed that mRNA of lactate dehydrogenase, chain M, was less abundant in four XP group A strains (extent of reduction: 70%) and in two XP group D strains (extent of reduction: 58%). Enzyme activity was also diminished. In addition, mRNA of the gene for glyceraldehyde-3-phosphate dehydrogenase was less expressed in the same XP group A and D fibroblast strains investigated (reduction in both complementation groups: 50%). Both glycolytic enzymes have nuclear functions apart from their role in sugar metabolism. Lactate dehydrogenase, chain M, is identical to a helix-destabilizing protein; it is closely associated with chromatin and unfolded DNA, suggesting a role in DNA synthesis and transcription. The 37-kDa subunit of glyceraldehyde-3-phosphate dehydrogenase is involved in transcription and was shown to be identical to uracil-DNA glycosylase, a base-excision repair enzyme. We presume that the nuclear functions of these glycolytic enzymes may be thwarted in the XP strains investigated and may account for malfunctions in XP, particularly for neurological disturbances.
J Cancer Res Clin Oncol 1994
PMID:Expression of mitochondrial genes and DNA-repair-related nuclear genes is altered in xeroderma pigmentosum fibroblasts. 820 43

The 28S rRNA, a ribosomal RNA, and the ACTB and GAPD mRNAs, coding respectively for beta-actin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), are frequently presented as controls of modulated gene expression. These transcripts were quantified by replicate slot-blot autoradiography and image analysis in mammary epithelial cells and fibroblasts from breast tissues. Each cell-type group comprised strains with different pathological backgrounds, growth rates, antigenic phenotypes and culture histories. The effects of a differentiating agent (cholera toxin) and/or a tumor promoter (12-O-tetradecanoyl-phorbol-13-acetate) were also examined. Despite the impression that visual examination of autoradiographs might create, image analysis suggests that 28S rRNA, ACTB and GAPD are substantially and independently influenced by the above biological factors and by the drugs. Therefore, these transcripts represent specifically regulated cellular activities and may not be taken as alternative indicators of the overall transcription rate or of the amount of material being examined. Instead, such nonspecific variation may be accurately measured and removed from quantitative data using a principal component function. A methodology that allows comparison of expression (or amplification) patterns between genes, between experiments or, even, between laboratories is presented with an example of quantification of transcripts related to cell-growth, differentiation, signaling and cancer.
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PMID:Problems related to the interpretation of autoradiographic data on gene expression using common constitutive transcripts as controls. 836 99

A 28-base phosphodiester triple helix-forming oligonucleotide, mostly G and A containing, targeted to a polypurine tract interrupted by a purine-pyrimidine inversion, situated upstream from the TATA box of the promoter of the human HER2 gene, was conceived by computer modeling. The "energetically best choice" was oligo 28(C), which formed the triple helix in vitro, as proved by gel retardation and Fourier transform infrared spectroscopy. When administered as a complex with lipofectin, fluorescence confocal microscopy and electrophoresis confirmed the delivery and persistence of this unprotected oligonucleotide inside MCF7 (breast cancer) cells. At a concentration of 2 microM, the oligonucleotide reduced within 6 h the HER2 mRNA level to 42% (Northern blot) but did not interfere with the transcription of a housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase. During the first day of administration at 0.22 microM, it lowered to 59% the HER2 protein in treated, as compared to nontreated, cells (ELISA). The effect was sequence specific when compared to that of five different negative controls, and it was target selective when compared to the expression of a related, nontargeted protein, the epidermal growth factor receptor. By day 2, the inhibitory effect was overcome by replenishment reactions.
Cancer Res 1996 Feb 01
PMID:Temporary ex vivo inhibition of the expression of the human oncogene HER2 (NEU) by a triple helix-forming oligonucleotide. 856 64


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