Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human intestinal mucins are large glycoconjugates (greater than 1,000,000 D) that coat the epithelium, serving to lubricate and protect. Apart from this physiologic function, mucins are important in that they are frequently altered in cancer; thus, they have potential usefulness as tumor markers. We have isolated mucins from human LS174T colon cancer cells and small intestine, deglycosylated these highly purified glycoconjugates, produced polyclonal antibodies to the apomucins, and used these antibodies to isolate two different types of cDNA clones that encode different apomucins. The first class of cDNA clones was isolated using antibodies to deglycosylated LS174T mucin. These cDNA, designated SMUC or MUC2, contain 69 nucleotide tandem repeats that encode a repetitive peptide that is extremely rich in threonine and proline. Northern blots using MUC2 cDNA as probes exhibit large (7,600 bases) and polydisperse hybridization bands. This gene is polymorphic within the human population and is located on chromosome 11. The second class of cDNA was isolated using antibodies to deglycosylated small intestinal mucin. These cDNA, designated SIB or MUC3, have 51 nucleotide tandem repeats that encode a threonine- and serine-rich repetitive peptide. This mucin also is encoded by a large, polydisperse message, but it is clearly distinct from MUC2 as it is located on chromosome 7. Both the MUC2 and MUC3 mucins are expressed in colonic tumors; however, the level of their expression is quite variable. Thus, at least two mucins are expressed by the human gastrointestinal tract. Elucidation of the regulation of these two genes will be important in understanding the physiology and pathophysiology of the human intestine.
 ...
PMID:The structure of human intestinal apomucins. 189 19

Isotopically labeled [( 3H]serine, [3H]proline, and [35S]sulfate) subendothelial cell basement membranes were used to determine the role of urokinase plasminogen activator (uPA) and its specific inhibitor plasminogen activator inhibitor 2 (PAI-2) in colon cancer cell extracellular matrix degradation. Recombinant PAI-2 irreversibly inhibited low and high molecular weight purified human uPA in addition to both colon cancer cell-associated and secreted uPA, particularly if pro-uPA had been preactivated. Two selected lines (COLO394 and LIM1215) preferentially degraded differently labeled matrices in a time- and plasminogen-dependent manner. This process was inhibitable by PAI-2 in the medium at levels which suggested that some degree of "shielding" of cell surface uPA from inhibitor occurred. The ability of PAI-2 to regulate the invasive phenotype of cells which express cell surface or receptor-bound uPA is discussed.
 ...
PMID:Inhibition of cancer cell urokinase plasminogen activator by its specific inhibitor PAI-2 and subsequent effects on extracellular matrix degradation. 211 45

Mucins synthesized in colonic cancer are known to be different from those in the normal colon; however, the biochemical differences between these mucins have not been defined. We have purified mucins from samples of nonneoplastic (normal) human colon and colon cancer and found that the carbohydrate content of the cancer-associated mucins is 48% of that in the normal colon, including significant reductions in galactose, N-acetylglucosamine, N-acetylgalactosamine, and fucose. By subjecting the mucins to alkaline degradation, we determined that there are 19% fewer oligosaccharide chains per milligram of cancer-associated colonic mucin than there are in mucins from normal colons. We also found a reduction in mean oligosaccharide chain length in cancer-associated mucin (5.83 carbohydrate residues per chain) compared with those derived from normal colons (10.2 residues). Total and individual amino acid contents were greater in cancer-associated mucins, with the exception of three amino acids (threonine, serine, and proline), two of which represent the O-linked glycosylation sites for glycoproteins. Thus, mucins are aberrantly glycosylated in colon cancer, both in terms of the number and mean chain length of the oligosaccharide moiety. Because of their relative abundance in colonic tissue, mucins appear to be useful molecular species in the study of the derangements in protein glycosylation that occur during neoplasia.
 ...
PMID:The carbohydrate composition of mucin in colonic cancer. 232 10

A high molecular weight, mucous glycoprotein (MG) from the pleural fluid of lung adenocarcinoma was purified by the DEAE-cellulose, gel-filtration and wheat germ agglutinin affinity chromatography. Protein portion of the molecule was composed of amino acids rich in serine, threonine and proline, but methionine and tyrosine concentrations were relatively low. About 65% of the weight, was composed of galactose, galactosamine, glucosamine, fucose and sialic acid. The gel-filtration pattern on Sepharose 4B revealed Mr greater than 10(6) Da. The SDS-PAGE pattern revealed a main band at the position of the Mr about 350 kDa under the reducing condition. Rabbit antibody against this molecule recognized mainly the peptide portion, and the radioimmunoassay (RIA) using the double antibody method was developed by this antibody. Serum MG level was low in healthy subjects and in benign diseases (0.8 +/- 0.7 U/ml; mean +/- SD and 1.1 +/- 2.3 U/ml, respectively). Thus, 3 U/ml was used as the cut-off value. The mean of serum MG levels and positive rates in malignant diseases were significantly high; 4.4 U/ml and 32.3% in lung cancer, 20.1 U/ml and 77.5% in pancreas cancer 11.6 U/ml and 64.3% in gastric cancer, 12.9 U/ml and 57.1% in hepatoma, 12.3 U/ml and 77.8 in colon cancer. Other malignancies such as ovarial and uterus cancer showed also high levels. Elevated values in these malignancies were observed frequently in patients with metastasis. On the other hand, the false positive cases were found in 10% of benign diseases. Determination of MG seems to be useful for the detection of several kinds of malignancies, but it is not adequately sensitive as a screening method for early cancer detection.
 ...
PMID:Clinical significance of mucin-like high molecular weight glycoprotein originated from lung cancer as tumor marker. 274 68

The structure of colonic mucin, which is thought to be important in several diseases, including ulcerative colitis and colon cancer, is poorly understood. Mucin was isolated from nude mouse xenografts of the LS174T colonic adenocarcinoma cell line by gel filtration and CsCl density gradient centrifugation. The isolated mucin had a high content of threonine, serine, and proline, with 28% of the total amino acids O-glycosylated. The carbohydrates present were fucose, sialic acid, galactose, N-acetyl-glucosamine, and N-acetyl-galactosamine in the ratio of 0.4:1.5:1.0:0.9:1.4. Rabbit antibodies were prepared that recognized primarily protein-dependent determinants. By DEAE-cellulose chromatography, the purified mucin was found to be heterogeneous, with three major components that had small differences in carbohydrate composition. LS174T was antigenically and chromatographically similar to mucins in colon cancer tissue specimens and in nonmalignant colonic mucosae.
 ...
PMID:Isolation and characterization of colon cancer mucin from xenografts of LS174T cells. 318 78

Mucin has been purified from nude mouse xenografts of SW1990 human pancreatic cancer cells. The mucin was eluted at the void volume of Sepharose CL-4B and was of density greater than 1.3 in CsCl gradients. The isolated mucin had a high content of threonine, serine, and proline, with 31% of the amino acid residues O-glycosylated. The average oligosaccharide composition was NeuAc1.8Fuc0.7Gal2.0GlcNAc1.7GalNAc1.4. Polyclonal rabbit antibodies prepared against the purified mucin recognized primarily mucin polypeptide, and there was extensive immunological cross-reaction between SW1990 pancreatic cancer mucin and LS174T colon cancer mucin. However, using carbohydrate-specific monoclonal antibodies, the two mucins were found to differ. SW1990 mucin had more Lewis, sialyl Lewis, and sialyl Lewis activity, while the colon cancer mucin had more sialyl T antigen. Since pancreatic mucins, whether from normal pancreas or pancreatic cancer, have not previously been well characterized, the availability of SW1990 pancreatic cancer mucin may be useful as a model for studying the expressing of organ-specific or cancer-associated antigens.
 ...
PMID:Pancreatic cancer mucin from xenografts of SW1990 cells: isolation, characterization, and comparison to colon cancer mucin. 322 46

Two types of human fibroblasts have been isolated from a patient with a colon cancer with metastasis, one type was derived from a healthy part of the colon, and the other one isolated from a metastasized lymph node close to the intestine. These fibroblasts have been characterized for their expression of collagens type I, III and IV, vimentin, fibronectin, alpha-smooth muscle actin, laminin and desmin. The effects of conditioned media of human colon cancer cell lines, HT29, SW1116, LS180 and HCT8R, on the metabolism of these fibroblasts were tested. All the conditioned media stimulate both types of fibroblasts, as reflected by their incorporation of radiolabelled methionine and proline. Normal fibroblasts were highly sensitive to the conditioned media as compared to the activated fibroblasts. Additionally, the production of TGF beta 1 by the four colorectal cancer cell lines has been quantified, and significant qualitative (production of latent and/or active form) and quantitative differences were observed. The effects of the conditioned media of the four tumoral cell lines and exogenous TGF beta 1 on the proliferation of the two types of fibroblasts were compared. Our data indicated that the two types of fibroblasts respond differently to TGF beta 1 whereas they are both growth stimulated by the conditioned media, apart from the LS180 conditioned medium. We conclude that if TGF beta 1 acts in the fibroblastic reaction, additional factors are required.
 ...
PMID:[Role of TGF beta 1 in the stromal reaction to human colonic tumors]. 817 75

Expression of the MUC2 mucin has been demonstrated in normal gastrointestinal and respiratory epithelium and in carcinomas of the gastrointestinal and respiratory tracts, breast, ovary, and bladder using RNA probes and (or) monoclonal antibodies reactive with peptide epitopes on the 23 amino acid tandem repeat. Mouse monoclonal antibodies 4F1 and 3A2 were previously obtained by immunization with mucin derived from the LS174T colon cancer cell line and a KLH conjugate of a synthetic MUC2 VNTR peptide. These antibodies react with distinct epitopes on synthetic VNTR peptides and with normal and malignant epithelial tissues. In the present study, we examined the biosynthesis of MUC2 in LS174T colon cancer cells, using these antibodies to immunoprecipitate labelled mucin. A very high molecular mass protein was immunoprecipitated following 1 min pulse labelling with [3H]threonine and [3H]proline. A slight increase in molecular mass was observed over the next 16 min; however, unlike the MUC1 mucin, there was no large difference in apparent molecular mass between the MUC2 protein precursor and fully processed mucin using separation by SDS-PAGE. O-Glycosylation began within 1 h of synthesis of the protein core. Mucin secretion into the culture medium was detected in the 2nd hour following synthesis and was largely completed within 4 h of synthesis. Secreted mucin was far less reactive with these monoclonal antibodies than the precursor protein.
 ...
PMID:Early steps in the biosynthesis of MUC2 epithelial mucin in colon cancer cells. 903 93

Accumulation of histo-blood group antigens such as Lewis b, Lewis Y and H in colon cancer is indicative of poor prognosis. It is accompanied by increase in alpha1,2fucosyl-transferase activity, a key enzyme for synthesis of these antigens. Using a model of colon carcinoma, we previously showed that alpha1,2fucosylation increases tumorigenicity. We now show that tumorigenicity inversely correlates with the cells' sensitivity to apoptosis. In addition, poorly tumorigenic REG cells independently transfected with three different alpha1,2fucosyltransferase cDNAs, the human FUT1, the rat FTA and FTB were more resistant than control cells to apoptosis induced in vitro by serum deprivation. Inversely, PRO cells, spontaneously tumorigenic in immunocompetent syngeneic animals and able to synthesize alpha1,2fucosylated glycans, became more sensitive to apoptosis after transfection with a fragment of the FTA cDNA in the antisense orientation. Expression of alpha1,2fucosyl-transferase in poorly tumorigenic REG cells dramatically enhanced their tumorigenicity in syngeneic rats. However, in immunodeficient animals, both control and alpha1,2fuco-syltransferase transfected REG cells were fully tumorigenic and metastatic, indicating that the presence of alpha1,2fucosylated antigens allowed REG tumor cells to escape immune control. Taken together, the results show that increased tumorigenicity mediated by alpha1,2fucosyl-ation is associated to increased resistance to apoptosis and to escape from immune control.
 ...
PMID:alpha1,2Fucosyltransferase increases resistance to apoptosis of rat colon carcinoma cells. 1076 25

The p53-dependent initiation of apoptosis is accompanied by the induction of proline oxidase (POX), a mitochondrial enzyme catalyzing the conversion of proline to pyrroline-5-carboxylate with the concomitant transfer of electrons to cytochrome c. However, the contribution of increased POX activity to apoptosis, if any, remains unknown. Using Adriamycin to initiate p53-dependent apoptosis, we showed that the expression of POX is up-regulated in a time- and dose-dependent manner in a human colon cancer cell line (LoVo). In cells expressing POX, the addition of proline increases reactive oxygen species (ROS) generation in a concentration-dependent manner; glutamate, a downstream product of proline oxidation, had no effect. Induction of POX was dependent on the p53 status of the cell. In the conditionally immortalized murine colonic epithelial cell line YAMC, where the p53 phenotype can be modulated by temperature, proline oxidase expression and ROS production could only be induced when the cells were phenotypically p53-positive. To confirm that the observed ROS production was not secondary to some other effect of p53, we also conditionally expressed POX in a p53-negative colon cancer line. Again, we found a proline-dependent ROS increase with POX expression. We hypothesize that proline oxidation supports the generation of ROS by donating reducing potential to an electron transport chain altered either by p53-dependent mechanisms or by overexpression of POX.
 ...
PMID:Proline oxidase, encoded by p53-induced gene-6, catalyzes the generation of proline-dependent reactive oxygen species. 1128 Jul 28


1 2 3 4 Next >>