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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The distribution of carcinoembryonic antigen (CEA) in human colonic cancer cells was compared to normal colonic epithelial cells by the recently introduced protein G-gold immunoelectron microscopy method. Immunostaining for CEA was obtained in glutaraldehyde-fixed tissues, but tissues fixed in osmium tetroxide failed to retain CEA immunoreactivity. In normal colonic mucosa CEA was found on the brush border and in the apical vesicles of the absorptive cells. The labeling was most intense in the cells lining the upper crypts and luminal surfaces. Mucin granules of goblet cells were also labeled. Well-differentiated adenocarcinoma cells showed cytoplasmic and apical labeling sites similar to those of normal colonic epithelial cells and in addition labeling of the basolateral membranes. The latter sites were more intensely labeled in poorly differentiated cancer cells whereas the intracytoplasmic reactivity was less intense compared to well-differentiated tumor cells. One case of poorly differentiated adenocarcinoma showed no labeling. These results indicate that the cellular site and intensity of CEA expression are closely associated with cellular differentiation in colonic cancer cells. The findings are consistent with the hypothesis that the biosynthesis and processing of CEA are different in colonic cancer cells as compared to normal colonic epithelial cells.
Exp Mol Pathol 1988 Dec
PMID:Protein G-gold immunoelectron microscopy of colon carcinoma: the effect of tumor differentiation on carcinoembryonic antigen immunostaining. 305 4

Retrovirus vector infection was used to introduce large numbers of unique genetic markers into tumor cell populations for the purpose of analyzing comparative changes in the clonal composition of metastatic versus that of nonmetastatic tumors during their progressive growth in vivo. The cell lines used were SP1, a nonmetastatic, aneuploid mouse mammary adenocarcinoma, and SP1HU9L, a metastatic variant of SP1. Cells were infected with delta e delta pMoTN, a replication-defective retrovirus vector which possesses the dominant selectable neo gene and crippled long terminal repeats. G418r colonies were obtained at a frequency of 4 x 10(-3). Southern blot analysis of a number of clones provided evidence of random and heritable integration of one or two copies of the proviral DNA. Clonal evolution of primary tumor growth and the nature of lineage relationships among spontaneous metastases and primary tumors were analyzed by subcutaneously injecting 10(5) cells from a pooled mixture of 3.6 x 10(2) G418r SP1HU9L or 10(4) G418r SP1 colonies into syngeneic CBA/J mice. The most striking finding was the relative clonal homogeneity of advanced primary tumors; they invariably consisted of a small number (less than 10) of distinct clones despite the fact that hundreds or thousands of uniquely marked clones had been injected. In the case of the metastatic SP1HU9L cells, the nature of these "dominant" clones varied from one tumor to another. Analysis of a number of lung metastases revealed that a proportion of them were derived from dominant primary tumor clones and were composed of one, and sometimes two, distinct progenitors. In some animals, all the lung metastases were derived from a common progenitor clone, whereas in others, each metastatic nodule had a different progenitor. The results show the following. (i) Retrovirus vector infection can be used to introduce large numbers of unique and stable clonal markers into tumor cell populations. (ii) The progeny of a very limited number of clones dominate in advanced primary tumors. (iii) Mammary carcinoma metastases are of mono- or biclonal origin. The significance of the results is discussed.
Mol Cell Biol 1988 Aug
PMID:Genetic tagging of tumor cells with retrovirus vectors: clonal analysis of tumor growth and metastasis in vivo. 321 Nov 40

Carcinoembryonic antigen (CEA) expression is perhaps the most prevalent of phenotypic changes observed in human cancer cells. The molecular genetic basis of this phenomenon, however, is completely unknown. Twenty-seven CEA cDNA clones were isolated from a human colon adenocarcinoma cell line. Most of these clones are full length and consist of a number (usually three) of surprisingly similar long (534 base pairs) repeats between a 5' end of 520 base pairs and a 3' end with three different termination points. The predicted translation product of these clones consists of a processed signal sequence of 34 amino acids, an amino-terminal sequence of 107 amino acids, which includes the known terminal amino acid sequence of CEA, three repeated domains of 178 amino acids each, and a membrane-anchoring domain of 27 amino acids, giving a total of 702 amino acids and a molecular weight of 72,813 for the mature protein. The repeated domains have conserved features, including the first 67 amino acids at their N termini and the presence of four cysteine residues. Comparisons with the amino acid sequences of other proteins reveals homology of the repeats with various members of the immunoglobulin supergene family, particularly the human T-cell receptor gamma chain. CEA cDNA clones in the SP-65 vector were shown to produce transcripts in vitro which could be translated in vitro to yield a protein of molecular weight 73,000 which in turn could be precipitated with CEA-specific antibodies. CEA cDNA clones were also inserted into an animal cell expression vector and introduced by transfection into mammalian cell lines. These transfectants produced a CEA-immunoprecipitable glycoprotein which could be visualized by immunofluorescence on the cell surface.
Mol Cell Biol 1987 Sep
PMID:Isolation and characterization of full-length functional cDNA clones for human carcinoembryonic antigen. 367 Mar 12

Sialomucins are abundant on the surfaces of certain ascites tumor cells and have been implicated in the escape of tumors from immune destruction and metastasis. They are large, highly glycosylated glycoproteins which are rich in serine and threonine and have a variety of 0-linked oligosaccharides. The sialomucin (ASGP-1) or 13762 rat mammary adenocarcinoma ascites cells represents more than 0.5% of the total cell protein and can be isolated from cell membranes by centrifugation in 4 M guanidine hydrochloride-cesium chloride. ASGP-1 can also be isolated from membranes or cells by nonionic detergent extraction as a 1:1 complex with a second glycoprotein ASGP-2. Studies with the fluorescent lectins peanut agglutinin, which binds ASGP-1, and Concanavalin A, which binds ASGP-2, indicate that the glycoproteins are present at the cell surface as a complex. ASGP-1 is shed into cell culture medium or ascites fluid, apparently by a proteolytic cleavage mechanism. 13762 ascites cells grown in culture or as solid tumors lose their ASGP-1. The sialomucin reappears with extensive passage of the tumor cells in ascites form. Studies on the biosynthesis of ASGP-1 indicate that carbohydrate is being added over nearly the entire period of transit of ASGP-1 from the site of polypeptide synthesis to the plasma membrane. The negatively charged, rod-like structure of the sialomucins suggests that they may play a role in inhibiting recognition or binding processes necessary for the immune destruction of these tumor cells.
Mol Cell Biochem
PMID:Structural and functional aspects of tumor cell sialomucins. 382 20

In the adenocarcinoma cell line HT-29 receptor-bound insulin is substrate for a proteolytic process leading to the release of about half of the cell-associated [125I]monoiodoinsulin in the form of [125I]iodide and [125I]monoiodotyrosine. Classical lysosomal inhibitors (NH+4, methylamine, leupeptin) did not inhibit this proteolysis. Inhibitors of membrane traffic (chloroquine and monensin) and of metabolism (CN-) inhibited the fractional receptor-mediated degradation. The former led to an increased cell-associated 125I activity whereas the latter reduced the uptake. Sulphydryl reagents inhibited the receptor-mediated degradation. The data are not compatible with a quantitatively major role of lysosomes in the receptor-mediated insulin degradation. However, since the process requires energy it is suggested that the receptor-mediated degradation takes place in vesicles other than secondary lysosomes. The responsible enzyme(s) may belong to the thiol group of proteases. Both insulin and the insulin receptor are internalized as a consequence of incubation of HT-29 cells with insulin.
Mol Cell Endocrinol 1985 Jan
PMID:Receptor-mediated degradation and internalization of insulin in the adenocarcinoma cell line HT-29 from human colon. 388 81

When glucose is added to the culture medium, some cells of the undifferentiated HT-29 line derived from a human colonic adenocarcinoma develop spherical structures, demonstrated to be intracellular by the ruthenium red staining method, which are bordered with microvilli, contain osmiophilic substances and resemble intracellular lumina. When glucose is replaced by galactose in the culture medium, the cells differentiate apical membranes bordered with microvilli. Our observations suggest that these new apical membranes correspond to the membranes of intracellular lumina which have opened outside the cells. We suggest that intracellular lumina may represent "compensation" for loss of polarity of epithelial cells and may be an important step in the repolarizing process of the cells.
Virchows Arch B Cell Pathol Incl Mol Pathol 1984
PMID:The role of intracellular lumina in the repolarization process of a colonic adenocarcinoma cell line. 615 May 75

NCA was purified from normal human lung (L-NCA) and from liver metastases of colon adenocarcinoma (T-NCA), L-NCA and T-NCA had different carbohydrate compositions, but showed an immunological identity in double immunodiffusion with the use of anti-CEA and anti-L-NCA sera. In SDS-polyacrylamide gel electrophoresis L-NCA and T-NCA showed similar molecular weights of about 110,000 and 120,000, respectively. However, if the samples were heated for 3 min at 100 degrees C in the presence of 1% SDS before electrophoresis, their apparent mol. wt decreased to about 50,000, suggesting the dissociation of NCA molecules into subunits. The dissociation of NCA was independent of the presence of mercaptoethanol and did not destroy the ability of NCA to precipitate with anti-CEA and anti-NCA sera. Besides NCA (and CEA in tumor tissue), the presence of a lower molecular weight cross-reacting antigen was observed in lung and tumour. Double immunodiffusion showed that this additional antigen was not a dissociated form of NCA.
Mol Immunol 1983 Jul
PMID:The subunit structure of non-specific cross-reacting antigen (NCA). 641 74

Human intraspecific hybrids were formed between tumor cells isolated from both primary and metastatic tumors and a tissue culture adapted cell line, D98OR, a HeLa derivative which is thioguanine and ouabain resistant. Five different tumor types in all were attempted: renal cell carcinoma, colon adenocarcinoma, melanoma, chrondrosarcoma, and hepatocarcinoma. The tumor tissue was either (1) immediately dissociated and fused, or (2) frozen and later thawed, dissociated, and fused. Two different PEG concentrations were used. The results reported here demonstrate that: (1) hybrid tumor cell lines can be made from several types of cancer, (2) unfrozen tumor tissue fused with D98OR by exposure to 50% PEG appears optimal, (3) chromosome loss, as determined by flow cytometry studies of hybrid DNA content, is minimal, and (4) hybrids have characteristics consistent with derivation from tumor cells rather than derivation from the nonmalignant cells of a tumor.
Somat Cell Mol Genet 1984 Mar
PMID:Somatic cell hybridization of human tumor samples. 658 90

Polymerase chain reaction (PCR) amplification has been used to determine the clonal composition of tissues based on analysis of the pattern of X-chromosome inactivation, but its use has been limited by technical difficulties. This report presents an expedited method to use PCR in the analysis of clonality. The method uses gel electrophoresis of heteroduplexes formed with an artificial heteroduplex generator (HG) and PCR products from the phosphoglycerate kinase-1 (PGK-1) gene from the tissue sections. Amplification was successful in 36 of 37 cases originally diagnosed as endometrial adenocarcinoma. HG analysis of 36 cases confirmed heterozygosity in 12 cases (33.3%). PGK-1 PCR amplification product was obtained from both control and lesional tissue in 10 of the 12 heterozygous cases. Of these 10 cases, seven were shown to consist of clonal cell populations by HG analysis. Two of three cases diagnosed as well-differentiated endometrioid adenocarcinoma were found to be comprised of polyclonal populations of cells. One case produced an anomalous pattern with HG analysis and was shown to be aneuploid by fluorescence in situ hybridization (FISH) with a chromosome X alpha-satellite probe. It is concluded that HG is a useful alternative to restriction fragment length polymorphism (RFLP) analysis of X-chromosome inactivation as a marker of tissue clonality in cases in women.
Diagn Mol Pathol 1995 Sep
PMID:Analysis of clonality by polymerase chain reaction for phosphoglycerate kinase-1. Heteroduplex generator. 749 37

The DHD/K12/PROb rat colonic epithelial cell line, which was originally derived from a chemically induced adenocarcinoma, expresses functional glucocorticoid receptors (GR) and has been reported to be growth inhibited by glucocorticoid agonists. In the present study the potential mechanisms underlying corticosteroid-mediated autoregulation of GR mRNA levels in this colonic cell line were investigated. The GR mRNA levels in the various treatment groups were quantitated via the ribonuclease protection assay using a specific 32P-cRNA probe. Time-course experiments demonstrated that in contrast to several other cell lines that are also growth inhibited by glucocorticoids, treatment of confluent monolayers of PROb cells with the pure GR agonist RU 28362 (1 microM) elicits a rapid and significant (65%) down-regulation of GR mRNA levels that is sustained for at least 36 h. This down-regulation, which is also elicited to a lesser extent by weaker GR agonists including corticosterone and aldosterone, is blocked by the GR antagonist RU 38486. The protein synthesis inhibitor cycloheximide was utilized to demonstrate that the initial phase (6 h) of agonist-mediated down-regulation occurs independently of ongoing protein synthesis, although new protein synthesis, perhaps of the GR protein itself, is required to maintain this down-regulation. Although agonist-mediated down-regulation in these cells probably occurs primarily at the level of GR gene transcription, inhibition of ongoing RNA synthesis with actinomycin D or 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) demonstrated that during the initial phase (1 h) of this down-regulation, but not following maximal (18 h) down-regulation, RU 28362 treatment also significantly reduces the stability of the GR mRNA.
J Steroid Biochem Mol Biol 1995 Nov
PMID:Potential mechanisms underlying autoregulation of glucocorticoid receptor mRNA levels in the DHD/K12/PROb rat colonic adenocarcinoma cell line. 749 1


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