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)

Type I transglutaminase (TGase I, keratinocyte or particulate transglutaminase) is a 92-kilodalton (kDa) protein expressed in abundance in cultured keratinocytes and in the hyperproliferative skin disorder psoriasis. To determine the expression of TGase I protein and mRNA, we studied tissue and established squamous carcinoma lines derived from different sources. Immunohistochemistry and Western blotting were used to detect TGase I protein with the B.C1 mouse monoclonal antibody. Only well-differentiated, skin-derived squamous carcinomas stained for TGase I. However, a precocious pattern of expression was seen overlying less-differentiated tumors. Compared to cultured human keratinocytes, squamous cell carcinoma (SCC) had many times less to 7.8 times more TGase I protein, greatest in the two most differentiated tumor lines 14-83 and ME-180. TGase I mRNA levels ranged from 0.010 to 0.00004 pg/microgram total RNA by reverse transcriptase-polymerase chain reaction using an internal standard. Protein expression correlated with mRNA levels in most SCC lines. When a human TGase I promoter was isolated and used to study genomic DNA, SCC1-83 was shown to have unique restriction enzyme fragments, including one indicative of methylation differences, also present within DNA from the KB line. These studies suggest that transcriptional control of TGase I gene expression in squamous carcinomas may be influenced both by cis elements in the promoter and by the degree of tumor squamous differentiation.
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PMID:Keratinocyte transglutaminase expression varies in squamous cell carcinomas. 790 83

Using 7,12-dimethylbenz[a]anthracene as the initiator and 12-O-tetradecanoyl-13-acetate as the tumor promoter on the dorsal skin of Sencar mice, we previously showed that pharmacological dietary all-trans-retinoic acid and beta-carotene inhibit the conversion of papillomas to carcinomas in a two-stage system of chemical carcinogenesis. The purpose of this study was to determine the influence of dietary retinoic acid and beta-carotene on retinoid and beta-carotene concentrations in skin and other tissues. We were unable to measure tissue retinoic acid because of the relatively limited amount of tissue available for analysis and the fast rate of metabolism. Different dietary levels of retinoic acid or beta-carotene did not influence total retinol of skin, papilloma, and carcinoma tissues, which all showed a concentration of approximately 1 +/- 0.5 microgram/g wet wt. Equally refractory to dietary retinoic acid or beta-carotene was serum retinol concentration. In contrast, dietary retinoic acid protected loss of liver retinol and retinyl palmitate, and beta-carotene caused an increase in beta-carotene and retinyl palmitate in liver but did not affect serum and liver retinol. We further investigated metabolic and functional aspects of retinoic acid in cultured mouse epidermal keratinocytes (LC-8 cells) and found that these cells actively metabolized [10,11-14C]retinoic acid to polar compounds. Isomers of retinoic acid were a minor product in the presence of cells and the major product when incubated in serum-containing medium in the absence of cells. From the functional point of view, exposure of LC-8 cells to 3 x 10(-6) M all-trans-retinoic acid (RA) caused a 75-fold induction in tissue transglutaminase and an approximately 9-fold induction in 10(-6) M RA at three days of culture. We conclude that retinoic acid spares endogenous retinol and that beta-carotene greatly enhances liver retinyl palmitate levels. Moreover we show that although mouse epidermal cells metabolize retinoic acid at a very high rate, they respond functionally by induction of tissue transglutaminase activity. Because this enzyme has been suggested to be involved in programmed cell death, we are presently investigating the possibility that it may be involved in the inhibition of carcinogenesis in mice fed pharmacological doses of RA.
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PMID:Retinol and beta-carotene concentrations in skin, papillomas and carcinomas, liver, and serum of mice fed retinoic acid or beta-carotene to suppress skin tumor formation. 791 Mar 92

Tissue type II transglutaminase (TGase) is a member of the TGase family that catalyzes Ca(2+)-dependent covalent cross-linking of several amines to the gamma-carboxamide group of protein-bound glutamine residues. The degree of therapeutic efficacy or toxicity of drugs may be related to their ability to serve as a substrate for TGase and their covalent linkage to glutamine residues of regulatory proteins through the catalytic action of this enzyme. Here, doxorubicin (adriamycin)-resistant human breast carcinoma MCF-7ADR cells exhibited 40- to 6C-fold higher TGase activity than control drug-sensitive MCF-7WT cells. The same was observed in vivo: a small proportion of tumor cells became positive for TGase after administration of adriamycin-based chemotherapy to patients with breast carcinoma. Similarly, continuous culture of MCF-7WT cells in the presence of adriamycin led to the appearance of the drug-resistant phenotype that was in turn associated with increased expression of TGase. This increase in TGase was specific for adriamycin resistance. Like most known TGase, MCF-7ADR TGase was completely dependent on the presence of Ca2+ for its catalytic activity. Based on its immunoreactivity, the TGase in MCF-7ADR cells was identified as an 85-kDa tissue-type TGase and was present only in the soluble form. Immunoblot analysis revealed that the increase in TGase activity was due to accumulation of the protein. Two cytosolic proteins of approximately 20 and 30 kDa in MCF-7 cells served as suitable acyl donor substrates in TGase-catalyzed reactions.
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PMID:High levels of transglutaminase expression in doxorubicin-resistant human breast carcinoma cells. 791 83

The identification of (gamma-glutamyl)polyamines in proteolytic digest of proteins from the cytosolic and particulate fractions of B16-F10 and B16-F10Lr6 cell lines, originating from a spontaneous tumor in C57BL/6 mice, indicates that polyamines are incorporated into melanoma cell proteins by transglutaminases (TGases-EC 2.3.2.13). The levels of spermidine-derived protein cross-links were found to be inversely related with the metastatic potential of the 2 melanoma lines. Characterization of TGase activity in the 2 tumor cell lines showed 3 types of enzyme. The soluble cellular TGase activity (TGase C) was higher, and increased more, during the growth of the least metastasizing clone B16-F10Lr6 than in the B16-F10 line, which is the most metastasizing. Consistently, N1,N8-bis(gamma-glutamyl) spermidine, which is responsible for protein cross-link formation, was present in greater amount in B16-F10Lr6 cells. The enhancement by theophylline of soluble-TGase activity and spermidine-dependent protein cross-links of B16-F10 cells reduced, with linear dose dependence, the ability of these cells to penetrate through human fibronectin-coated membrane in an in vitro assay of invasiveness. Our data confirm and extend earlier observations indicating that the propensity of a tumor to metastasize can be indirectly related to intracellular levels of TGase activity, and provide the basis for some speculation concerning the role of polyamines as modifiers of murine melanoma cell proteins in metastasis.
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PMID:Differences in the post-translational modification of proteins by polyamines between weakly and highly metastatic B16 melanoma cells. 809 90

Transglutaminases with different functions and tissue distribution patterns can be distinguished by specific antibodies and by inhibition of enzyme activity in the presence of guanosine triphosphate (GTP). The most common form is the so-called tissue-type transglutaminase that is apparently involved in membrane stabilization processes, e.g. during apoptosis, and can be inhibited by incubation with GTP at low calcium concentrations. A secretory transglutaminase that cannot be inhibited by GTP is synthesized in an androgen-dependent manner in the dorsal prostate of the rat, the site suggested to represent the origin of the Dunning tumor used as an experimental model in prostate cancer research. Here we studied the expression of transglutaminases in different Dunning tumor lines--mainly in the highly differentiated H subline--and characterized the enzyme both biochemically and immunocytochemically. A very high enzyme activity was found only in the less well differentiated HI-F tumor line. Immunohistochemical reactions and Western blot analysis showed that there is no secretory transglutaminase present in any of the Dunning tumor lines studied. Transglutaminase activity of the Dunning tumor results from the so-called tissue-type enzyme that is non-organ specific. The absence of a secretory form of transglutaminase does not support the contention of a prostatic origin of the Dunning tumor.
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PMID:Tissue-type transglutaminase expression in the Dunning tumor. 809 3

A large molecular weight sodium dodecyl sulfate (SDS)-insoluble polymer was isolated from rat liver and shown to be a product of transglutaminase activity by virtue of its high epsilon(gamma glutamyl)lysine content. Antiserum raised against this polymer crossreacted with another product of transglutaminase activity, the apoptotic envelope isolated from cultured hamster fibrosarcoma cells. The amino acid composition of isolated apoptotic envelopes and the SDS-insoluble polymer were found to be comparable, although not identical. Using the polymer antiserum, the apoptotic index (mg polymer protein per mg DNA) of normal and tumor tissue was determined and found to correlate with the associated transglutaminase activity. Localization of proteins involved in polymer formation in neonatal rat liver cells was found immunohistochemically to be in those cells undergoing apoptosis; these cells also stained selectively for transglutaminase. Several proteins from liver homogenate were found to crossreact with the antipolymer serum, notably proteins of 120, 80, 43 and 38 kDa.
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PMID:Characterization of the transglutaminase-mediated large molecular weight polymer from rat liver; its relationship to apoptosis. 809 61

Cell lineage and cell function antigens were studied immunohistochemically in human immunodeficiency virus-associated oral Kaposi's sarcoma to provide insight into tumor pathogenesis. All tumors were composed predominantly of spindle cells that expressed endothelium-associated antigens, CD34 and CD36 (factor VIII-related antigen was expressed by considerably fewer numbers of tumor cells). Infrequently, spindle tumor cells also expressed actin. Factor XIIIa positive spindle and dendritic stromal cells comprised up to 9% of the tumor cell population. Other spindle and dendritic cells expressing macrophage-associated antigen, CD68, accounted for up to 15% of the tumor cells. Mast cells occurred frequently within and around tumors. Leukocyte function antigen (CD18) was expressed by approximately 13% of tumor cells, and its ligand, intercellular adhesion molecule (ICAM), was expressed by some tumor-associated capillaries (which also expressed endothelial leukocyte adhesion molecule, ELAM) and occasional stromal cells. Staining for proliferating cell nuclear antigen was noted in both interstitial and vascular lining cells. All tumors were non-reactive for human Papillomavirus antigen and HIV p24 antigen. Oral KS is a heterogeneous cellular proliferation composed predominantly of endothelial or endothelium-related spindle cells. Other spindle/dendritic (XIIIa-positive and CD68-positive) cells and mast cells are also present and may contribute to tumor development. ICAM and ELAM expression within tumors may assist infiltration of macrophages and other inflammatory cells into these lesions.
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PMID:Human immunodeficiency virus-associated oral Kaposi's sarcoma. A heterogeneous cell population dominated by spindle-shaped endothelial cells. 810 Apr

Yoshida tumor cells contain consistent amounts of type 2 transglutaminase, along with a membrane bound form of the enzyme. Digitonin permeabilized cells retain a large proportion of type 2 TGase and of substrate proteins which are labelled by radioactive putrescine in the presence of calcium. GTP inhibits protein labelling at low calcium concentration by inhibiting type 2 TGase without affecting membrane-bound TGase. These results support the notion that inhibition of type 2 TGase by GTP is physiologically relevant.
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PMID:Regulation of transglutaminase activity by GTP in digitonin permeabilized Yoshida tumor cells. 810 19

Sialic acid-binding lectin (SBL-C) from Rana catesbeiana eggs inhibits the growth of tumor cells such as P388 and L1210 leukemia cells (K. Nitta et al., Cancer Res., 54: 920-927, 1994). Here we report the establishment of an SBL-resistant P388 variant cell line, RC-150. Both P388 and RC-150 cells were agglutinated by SBL-C; however, growth of RC-150 cells was unaffected by SBL-C. Cytoplasmic free Ca2+ concentration and transglutaminase activity of RC-150 cells were 0.5 (110 nM) and 3 times (0.62 nmol/mg/min) as high as those of P388 cells, respectively. Microvilli and microplicae were observed on the surface of P388 cells by scanning electron microscopy but were rarely seen on RC-150 cells. Dansylcadaverine-labeled SBL-C bound to both P388 and RC-150 cells. Binding of SBL-C to these tumor cells appears to be mediated by two species of wheat germ agglutinin-stained cell membrane sialoglycoproteins. Labeled SBL-C entered P388 but not RC-150 cells, suggesting that internalized SBL-C acts as an inhibitor of cell proliferation.
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PMID:Characterization of a Rana catesbeiana lectin-resistant mutant of leukemia P388 cells. 831 83

Using pre-confluent cultures of a human colon tumor cell line deficient in transglutaminase (LS174T cells), we have investigated the effect of adding exogenous transglutaminase (TGA) on cell spreading. The cells were plated at either 4.5 x 10(5) cells per well (low-seeded cultures) or 9 x 10(5) cells per well (high-seeded cultures) in 24-well dishes and treated for either 1 or 4 days (low- and high-seeded cultures respectively) under following conditions: Chee's Essential Medium (CEM) + 10% fetal calf serum (FCS); CEM + 10% FCS + TGA; CEM + 10% FCS + dithiothreitol (DTT) + CaCl2; CEM + 10% FCS + DTT + CaCl2 + TGA. Photomicrography of the cells after these treatments revealed that in both low- and high-seeded cultures, TGA inhibited the spreading of the cells both in the presence and absence of DTT and calcium. Individual colony sizes were significantly smaller in the presence of TGA. This phenomenon may be related to the ability of TGA to promote cell interactions with the underlying tissue matrices and metastasis.
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PMID:Effects of exogenous transglutaminase on spreading of human colorectal carcinoma cells. 852 78


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