Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Humoral hypercalcemia of malignancy (HHM) is at least partly caused by tumor secretion of PTH-related peptide (PTHrP), but there is growing evidence for cosecretion with PTHrP of other bone-resorbing peptides, such as the cytokine interleukin-1 alpha (IL-1 alpha). Administration of PTHrP in vivo and in vitro generally mimics the actions of PTH itself, with increases in both resorption and formation of bone. However, bone in HHM is characterized by uncoupling of bone turnover, with increased resorption and decreased formation. We performed experiments to determine whether IL-1 alpha might alter the effects of PTHrP and produce uncoupling. Thus, we administered to 100-g male rats by sc osmotic minipumps synthetic PTHrP-(1-34) alone (2 micrograms/100 g/day), recombinant IL-1 alpha alone (1.5 micrograms/100 g/day), both peptides together at the previous doses, or vehicle only. We infused 5 groups of 12 rats each (PTHrP, IL-1 alpha, PTHrP plus IL-1 alpha, ad libitum fed control, and controls pair-fed to the PTHrP plus IL-1 alpha group) for 14 days. At the end of the study, blood and urine were taken for chemical measurements, and tibias and femurs were harvested for histomorphometry and extraction of RNA from periosteal cells. As expected, PTHrP induced hypercalcemia, relative hypophosphatemia, phosphaturia, and reduced bone mass. Osteoblast number was increased, but osteoclast number was not. Indices of bone formation were unchanged or reduced. The dose of IL-1 alpha chosen had no statistically significant effect, except for reduced longitudinal bone growth, but when combined with PTHrP, IL-1 alpha reduced hypercalcemia, hypophosphatemia, and phosphaturia. In contrast to the blood and urine effects, IL-1 alpha did not interact significantly with PTHrP's effect on bone measurements. Northern analysis of periosteal cell mRNA showed that PTHrP reduced expression of osteocalcin, but not glyceraldehyde-3-phosphate dehydrogenase; IL-1 alpha had no additional effect. These data suggest that 1) continuously administered PTHrP alone may induce uncoupled bone turnover with decreased cortical bone formation; 2) IL-1 alpha appears to inhibit strongly the renal effects of PTHrP and weakly (if at all) its actions on bone and, thus, to decrease its hypercalcemic, phosphaturic, and hypophosphatemic actions; and 3) cosecretion of IL-1 alpha, and possibly other peptide cytokines, with PTHrP may modify the clinical expression of HHM.
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PMID:Inhibition by human interleukin-1 alpha of parathyroid hormone-related peptide effects on renal calcium and phosphorus metabolism in the rat. 131 27

The nearly complete amino acid sequence obtained for murine calcyclin from Ehrlich ascites tumor cells reveals a very strong similarity with the rat and human sequences previously deduced from corresponding cDNA clones. While mouse and rat calcyclins are identical, the human protein shows at three positions a conservative amino acid replacement. Using a mouse calcyclin affinity matrix, two proteins with molecular masses of about 36 kDa have been purified from Ehrlich ascites tumor cells. The interaction between these two proteins and the immobilized calcyclin is strictly Ca2(+)-dependent. Immunological criteria and partial sequence data identify the two calcyclin-binding proteins as the phospholipid-binding protein annexin II (p36) and the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase. These observations suggest that calcyclin may exert its physiological function by a Ca2(+)-dependent interaction with cellular targets, e.g. annexin II or glyceraldehyde-3-phosphate dehydrogenase.
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PMID:Characterization of the cell-cycle-regulated protein calcyclin from Ehrlich ascites tumor cells. Identification of two binding proteins obtained by Ca2(+)-dependent affinity chromatography. 199 97

Autocrine and paracrine modulation of transforming growth factor expression was assessed in rat intestinal epithelial cell lines designated IEC-6 and IEC-7. Addition of the transforming growth factor alpha (TGF alpha) homologue epidermal growth factor (EGF) to media of subconfluent IEC-6 cells led to autocrine stimulation of TGF alpha expression as well as increased expression of the transforming growth factor beta 1 (TGF beta 1). Increased expression of TGF alpha was maximal between 3 and 6 h after addition of EGF and subsequently declined coincident with increasing level of expression of TGF beta 1, which achieved maximal levels 6 h after addition of EGF and was sustained for more than 12 h. Addition of TGF beta 1 also led to autocrine induction of its own expression coincident with suppression of TGF alpha expression. Addition of TGF beta 1 was associated with increased expression of beta-actin when standardized to a constitutive transcript (GAPDH). Similar responses to addition of EGF and TGF beta 1, were observed in another intestinal epithelial cell line, designated IEC-17. Modulation of expression of TGFs was attenuated when cells were grown on the complex extracellular matrix produced by the Engelbreth-Holm-Swarm tumor (Matrigel), reflecting the baseline induction of TGF beta 1 expression when compared to IEC-6 and IEC-17 cells maintained on plastic. These observations suggest that expression of TGFs is controlled by autocrine mechanisms in intestinal epithelial cell lines and proliferation stimulated by TGF alpha may be initially self-reinforcing but ultimately downregulated by induction of TGF beta 1.
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PMID:Regulation of transforming growth factor expression in rat intestinal epithelial cell lines. 204 Jul 2

The histogenesis of chemically induced mouse lung adenomas is currently being debated. Tumors induced by a variety of chemicals and in a number of different strains exhibit growth patterns having a solid/alveolar appearance, a papillary appearance, or a mixture of both. Ultrastructural observations suggest that solid tumors are derived from the alveolar type II pneumocyte and that papillary tumors arise from the bronchiolar Clara cell. However, recent immunocytochemical investigations have concluded that most mouse lung tumors are derived solely from the alveolar type II cell. Enzyme histochemical methods have previously been utilized to identify Clara cells in pulmonary cell isolates and also to characterize mouse lung tumors. This report demonstrates a difference in glyceraldehyde-3-phosphate dehydrogenase (G3PD) activity in type II pneumocytes and Clara cells. Solid tumors and type II cells appear to have a similar G3PD activity, and this activity is different from that observed in papillary tumors and bronchiolar cells. These findings support morphological evidence that suggests mouse lung tumors are phenotypically different and may arise from at least two different cells of origin.
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PMID:Glyceraldehyde-3-phosphate dehydrogenase and other enzymatic activity in normal mouse lung and in lung tumors. 205 29

Complementary DNA clones representing genes in SENCAR mouse epidermis, the expression of which is induced 4 h after one topical application of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) were isolated. Of 56 isolated complementary DNA clones, 32 were identified to be identical to either metallothioneins (MT-I and MT-II) or endogenous retroviral like (VL30) sequences. In situ hybridization and analysis of mRNA levels in cell fractions separated by density gradient centrifugation revealed that MT induction was restricted to keratinocytes in the basal cell layer. Immunohistochemistry and time-kinetic studies on mRNA levels in mouse epidermis showed that the increase in MT and VL30 RNAs coincide in time with a TPA-induced transient block in basal cell proliferation (3-12 h after TPA treatment). MT immunoreactivity and transcript levels had returned to control values at a time point (24 h after treatment) when epidermis is known to hyperproliferate. Treatment with other types of tumor promoters showed that MT-I and MT-II mRNAs were coordinately induced and indicated that sn-1,2-dioctanoylglycerol, 12-O-retinoylphorbol-13-acetate, and mezerein induced MT to a lesser degree than TPA. The calcium ionophore A23187 induced mRNA levels for MTs as well as VL30. VL30 and MT mRNA levels were not found to be elevated in epidermal tumors whereas the mRNA level corresponding to glyceraldehyde-3-phosphate dehydrogenase was elevated in tumors and induced by TPA with time-kinetics that correlate with a TPA-induced hyperproliferation. These complementary DNA clones provide useful tools in the study of the gene-regulating effects of TPA in a target tissue relevant for tumor promotion.
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PMID:Isolation and characterization of complementary DNA clones corresponding to genes induced in mouse epidermis in vivo by tumor promoters. 210 42

We have examined expression of the smg p25A (a ras p21-like GTP-binding protein) gene in neural crest-derived tumor cell lines and neuroblastoma tissues. The human neuroblastoma cell lines GOTO, IMR-32, NB-1, and SK-N-SH expressed the 1.6-kilobase smg-25A mRNA. SH-SY5Y and SH-IN, variant cell lines with a neuronal phenotype derived from SK-N-SH, expressed much more smg-25A mRNA than did SH-EP1, a variant line with an epithelium-like phenotype also derived from SK-N-SH. The primitive neuroectodermal tumor cell lines SK-N-MC and KU-SN and the Ewing's sarcoma cell lines RD-ES and SK-ES expressed the smg-25A mRNA to a much smaller extent than did neuroblastoma cell lines. Of 15 human neuroblastoma specimens tested, 13 expressed the smg-25A mRNA to various extents. When the relative ratio of the smg-25A mRNA level to the glyceraldehyde-3-phosphate dehydrogenase mRNA level was compared among neuroblastoma tumor tissues, the value was significantly higher in tumors histologically diagnosed as ganglioneuroblastoma. The smg-25A mRNA was not detected in the tissues of Hodgkin's lymphoma, Wilms' tumor, Ewing's sarcoma, or undifferentiated sarcoma of the liver. These results suggest that the smg-25A mRNA level is closely related to the neuronal differentiation state of tumors derived from the neural crest.
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PMID:Expression of the smg p25A (a ras p21-like GTP-binding protein) gene in human neuroblastoma cell lines and tumor tissues. 212 31

A protein which binds to tubulin polymer was isolated from a human colonic tumor cell line. This protein has a molecular mass of 35 kDa, as determined by polyacrylamide slab gel electrophoresis. The protein was purified by affinity chromatography on taxol-stabilized microtubules, and it did not cross-react with anti-MAP2 or anti-tau antibodies. This protein was identified as glyceraldehyde-3-phosphate dehydrogenase by its enzyme activity and immunoblotting experiments. The purified protein caused a pronounced enhancement in the turbidity increase produced by in vitro tubulin polymerization, and electron microscopic observations revealed the presence of bundles of microtubules.
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PMID:Glyceraldehyde-3-phosphate dehydrogenase is a microtubule binding protein in a human colon tumor cell line. 273 53

The proliferation of in vitro grown Ehrlich ascites tumor cells is inhibited by pyruvate concentrations greater than 2 mM. In the presence of 4-5 mM pyruvate the growth is reduced to about 50%, in the presence of 20 mM to about 5-10%. Viability of the cells is not severely affected. Increase of DNA corresponds to the cell growth. On recultivation in pyruvate free standard medium, growth is nearly normal. Flow cytometric analyses of the proliferation kinetics of the cells in the presence of 20 mM pyruvate revealed a retardation of the passage of all phases of the cell cycle. No phase specific effects could be detected though the S- and G2M-phase are more afflicted than G1. The growth inhibition of EAT cells by pyruvate seems to depend on the presence of glucose. Exogenous pyruvate (greater than 1-2 mM) causes an activation of pyruvate dehydrogenase, a reduction of lactate production from glucose and a stimulation of lipid biosynthesis; the NAD/NADH ratio of the cells is reduced and a rise of glycolytic intermediates beyond glyceraldehyde-3-phosphate dehydrogenase is observed. Maximal activation of pyruvate dehydrogenase by non toxic concentrations of dichloroacetate is also accompanied by an inhibition of cell growth. It is suggested that an increase of glyceraldehyde-3-phosphate level and the changes in the redox state of the cells are of relevance for the inhibition of cell growth by pyruvate. 100-500 microM exogenous glyceraldehyde-3-phosphate strongly inhibited cell growth.
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PMID:Proliferation kinetics and metabolic features of in vitro grown Ehrlich ascites tumor cells in the presence of exogenous pyruvate. 294 14

Human lung cancers of all histological types contain a protein of 37,000 daltons (37K) as an abundant component. Partial sequence analysis of purified 37K revealed a strong homology with glyceraldehyde-3-phosphate dehydrogenase (GAPDH, EC 1.2.1.12). Tryptic peptide mapping analysis showed that the pattern of 37K was very similar to those of GAPDHs both purified from lung tumor and obtained commercially. An antibody raised against 37K in a rabbit also reacted with authentic GAPDH. These results suggest a possible involvement of GAPDH itself or a GAPDH-related protein in lung tumorigenesis.
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PMID:Similarity between glyceraldehyde-3-phosphate dehydrogenase and a 37,000-dalton protein which is abundantly expressed in human lung cancers. 308 88

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.
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PMID:Increased glyceraldehyde-3-phosphate dehydrogenase gene expression in human pancreatic adenocarcinoma. 318 54


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