Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mouse FM3A mammary adenocarcinoma cells exposed to the specific thymidylate synthetase (TS) inhibitor 10-propargyl-5,8-dideazafolate (PDF) responded by overproducing TS up to 200-fold. In the absence of inhibitor, the elevation of TS levels decayed with a half-life of about 4 weeks. Southern blot analysis of restricted DNA from the PDF-resistant cells using a TS-specific probe showed that the TS gene was amplified to the same extent as enzyme levels. The PDF-resistant cells showed moderate cross-resistance to growth inhibition by 5-fluoro-2'-deoxyuridine, which increased with TS overproduction, but cross-resistance to 5-fluorouracil (FUra) was less (2- to 3-fold) and did not change with increased TS levels. TS activity, measured as release of tritium from [5-3H]2'-deoxyuridine, was no higher in the intact PDF-resistant cells than in wild-type cells. Inhibition of TS activity by FUra in the wild-type cells was accompanied by a proportional decrease in the amount of free TS, presumably due to formation of the tight binding complex of TS with 5-fluoro-2'-deoxyuridylate and 5,10'-methylenetetrahydrofolate. However, in the PDF-resistant cells, most the TS was still in the free form even though TS activity was substantially (85-90%) inhibited. Addition of folinic acid did not change either the sensitivity of the cells to FUra or the rates of tritium release in the cells having overproduced TS. These results are consistent with compartmentalization of TS, possibly in a multienzyme complex.
Mol Pharmacol 1989 Aug
PMID:Activity of thymidylate synthetase and its inhibition by 5-fluorouracil in highly enzyme-overproducing cells resistant to 10-propargyl-5,8-dideazafolate. 252 57

Transgenic mice carrying the v-Ha-ras oncogene under the control of the mouse mammary tumor virus long terminal repeat were produced. These mice exhibit several phenotypes: mammary tumors, bilateral hyperplasia of the harderian lacrimal gland, primary bronchio-alveolar lung adenocarcinoma, and splenomegaly. High levels of the transgene RNA were detected in mammary, harderian, and lung tumors. Accumulation of cells of the myeloid lineages was found in enlarged spleens. This phenotype may represent an indirect effect of v-Ha-ras expression on myeloid progenitors. Our data illustrate the cell-specific effects of v-Ha-ras.
Mol Cell Biol 1989 Feb
PMID:Transgenic mice carrying the mouse mammary tumor virus ras fusion gene: distinct effects in various tissues. 254 Apr 27

Two new human cell lines, RCM-1 and CoCM-1, have been established from primary colorectal adenocarcinomas. Both cell lines were unique in that the cultures secreted trypsin inhibitors in vitro. The activities of these inhibitors were accumulated in serum-free media of both cell lines over a period of several days. Two inhibitors (PI-1 and PI-2) were isolated from serum-free conditioned medium in which RCM-1 was grown by anion-exchange and gel filtration high-performance liquid chromatography. PI-1 inhibited trypsin and chymotrypsin strongly, and pancreatic elastase weakly. Its molecular weight was about 57 kilodaltons (Kd) as determined by gel filtration chromatography. It cross-reacted with the antiserum elicited against human alpha 1-antitrypsin in double immunodiffusion. PI-1 corresponding to alpha 1-antitrypsin was also demonstrated immunohistochemically in both cell lines. PI-2 inhibited trypsin strongly, and chymotrypsin, kallikrein and plasmin weakly. It had higher molecular weight (200-300 Kd) than that of PI-1, and did not cross-react with antisera against human alpha 1-antitrypsin, alpha 2-macroglobulin, alpha 1-antichymotrypsin, alpha 2-plasmin inhibitor, inter-alpha-trypsin inhibitor and urinary trypsin inhibitor. RCM-1 and CoCM-1 are the first colorectal adenocarcinoma cell lines that secrete functionally active trypsin inhibitors, including alpha 1-antitrypsin in vitro, and are useful for the study of tumor-cell derived proteinase inhibitors.
Virchows Arch B Cell Pathol Incl Mol Pathol 1989
PMID:New human colorectal carcinoma cell lines that secrete proteinase inhibitors in vitro. 257 Apr 82

DNAs from 37 human gastric carcinomas and seven lymph node metastases were analyzed for alterations of the epidermal growth factor receptor (EGFR) gene and oncogenes by the Southern blot hybridization method. The probes used were EGFR gene, c-Ha-ras, v-Ki-ras, N-ras, c-myc, v-myb, v-fos, c-erbB-2, v-erbA, v-abl and v-fes. Amplification of the EGFR gene was detected in only one poorly differentiated adenocarcinoma. Amplifications of c-myc gene and c-erbB-2 gene were each observed in two well differentiated adenocarcinomas. One of these tumors had coamplification of c-erbB-2 and c-erbA genes but there were no amplifications nor rearrangements of other oncogenes. The poorly differentiated adenocarcinom with amplified EGFR gene also showed enhanced expression of EGFR gene by Northern blot analysis and additionally had strong synchronous immunoreactivity for EGFR and EGF.
Virchows Arch B Cell Pathol Incl Mol Pathol 1989
PMID:Amplification of epidermal growth factor receptor (EGFR) gene and oncogenes in human gastric carcinomas. 257 Apr 89

Three of 16 human gastric adenocarcinoma samples, maintained as solid tumors in nude mice, were found to carry amplified c-myc genes. In two samples with a high degree of c-myc DNA amplification (15- to 30-fold), double minute chromosomes were observed in karyotype analysis. The level of c-myc RNA was markedly elevated in a rapidly growing and poorly differentiated tumor, whereas it was only slightly elevated in a slowly growing and more differentiated tumor.
Mol Cell Biol 1985 Feb
PMID:Amplification and expression of a cellular oncogene (c-myc) in human gastric adenocarcinoma cells. 257 23

The effect of indomethacin on murine lymphokine-activated killer (LAK) cell activity was investigated using a natural killer-resistant, spontaneously developed, weakly immunogenic, and highly tumorigenic syngeneic murine mammary adenocarcinoma, mimicking that of human disease, as the target. When used in combination with human recombinant interleukin-2 (rIL-2), indomethacin was found to augment LAK cell activity, which was generated from culture of the normal mouse splenocytes with rIL-2, as compared to that with rIL-2 alone. This increase in LAK cell activity was shown to be indomethacin dose-dependent, and was demonstrated only when indomethacin was added to the rIL-2-containing medium at the beginning of culture. The enhancement of LAK cell activity by indomethacin was abrogated when the nylon-wool nonadherent "macrophage-poor" splenocytes were incubated with rIL-2 plus indomethacin. These results indicated that the rIL-2-induced LAK cell activity generated from murine splenocytes could be augmented by indomethacin, and the macrophages may be involved as the mediator.
Mol Biother 1989
PMID:Augmentation of murine lymphokine (rIL-2)-activated killer cell activity by indomethacin. 261 Sep 50

Azatyrosine [L-beta-(5-hydroxy-2-pyridyl)-alanine], an antibiotic isolated from Streptomyces chibanensis, inhibited the growth of NIH 3T3 cells transformed by the activated human c-Ha-ras gene but did not significantly inhibit the growth of normal NIH 3T3 cells. Surprisingly, upon treatment with azatyrosine most of the transformed cells apparently became normal. These apparently normal cells, named revertant cells, grew in the presence of azatyrosine and stopped growing when they reached confluency, and their normal phenotype persisted during prolonged culture in the absence of azatyrosine. The revertant cells did not grow in soft agar and scarcely proliferated in nude mice. The human c-Ha-ras gene present in transformed NIH 3T3 cells was still present in the revertant cells and was expressed to the same extent as in the original transformed cells, producing the same amount of activated p21. Treatment with azatyrosine caused similar conversion of NIH 3T3 cells transformed by activated c-Ki-ras, N-ras, or c-raf to apparently normal cells, but NIH 3T3 cells transformed by hst or ret were not exclusively converted by azatyrosine. Human pancreatic adenocarcinoma cells, which are known to contain an amplified activated c-Ki-ras gene and an amplified c-myc gene, were also converted to flat and giant revertant cells by treatment with azatyrosine.
Mol Carcinog 1989
PMID:Permanent conversion of mouse and human cells transformed by activated ras or raf genes to apparently normal cells by treatment with the antibiotic azatyrosine. 267 4

Transforming growth factor beta (TGF beta) is a multifunctional polypeptide that regulates proliferation, differentiation, and other functions of many cell types. The pathway of TGF beta signal transduction in cells is unknown. We report here that an early effect of TGF beta is an enhancement of the expression of two genes encoding serum- and phorbol ester tumor promoter-regulated transcription factors: the junB gene and the c-jun proto-oncogene, respectively. This stimulation was observed in human lung adenocarcinoma A549 cells which were growth inhibited by TGF beta, AKR-2B mouse embryo fibroblasts which were growth stimulated by TGF beta, and K562 human erythroleukemia cells, which were not appreciably affected in their growth by TGF beta. The increase in jun mRNA occurred with picomolar TGF beta concentrations within 1 h of TGF beta stimulation, reached a peak between 1 and 5 h in different cells, and declined gradually to base-line levels. This mRNA response was followed by a large increase in the biosynthesis of the c-jun protein (AP-1), as shown by metabolic labeling and immunoprecipitation analysis. However, differential and cell type-specific regulation appeared to determine the timing and magnitude of the response of each jun gene in a given cell. In AKR-2B and NIH 3T3 cells, only junB was induced by TGF beta, evidently in a protein synthesis-independent fashion. The junB response to TGF beta was maintained in c-Ha-ras and neu oncogene-transformed cells. Thus, one of the earliest genomic responses to TGF beta may involve nuclear signal transduction and amplification by the junB and c-jun transcription factors in concert with c-fos, which is also induced. The differential activation of the jun genes may explain some of the pleiotropic effects of TGF beta.
Mol Cell Biol 1989 Mar
PMID:Enhanced jun gene expression is an early genomic response to transforming growth factor beta stimulation. 272 96

The metabolism of the tropine indole-3-carboxylate ICS 205-930 (ICS), a highly potent and selective antagonist of 5-HT3 receptors, was investigated in continuous cell lines derived from rat or human liver and compared to the in vivo metabolism in rat and human. The well-differentiated rat hepatoma line 2sFou extensively metabolized ICS by hydroxylation of the indole moiety and subsequent conjugation to form the corresponding glucuronides and sulfates. The 2sFou cells also oxidized ICS at the tropinyl moiety to form both N-demethyl and N-oxide derivatives. The relative amount of the various metabolites was dependent on the substrate concentration. Pretreatment of the cells with dexamethasone increased the rate of metabolism for all pathways, while benz[a]anthracene caused an increase in hydroxylation at the indole moiety at the expense of N-oxidation. Phenobarbital pretreatment had no effect on ICS metabolism. The pattern of metabolites formed in 2sFou cells was qualitatively similar to that formed in rat urine. The human hepatoma line HepG2 metabolized ICS only to a small extent. The HepG2 cells failed to form detectable amounts of ICS conjugates found in human urine. The N-oxide-ICS was not found in HepG2 cells or in human urine. Virtually no ICS metabolites were found in human lung adenocarcinoma lines NCI-H358 or NCI-H322. The results suggest that continuous cell lines such as the differentiated rat hepatoma cells 2sFou might be used to mimic the metabolism of xenobiotics in rat and to clarify their complex metabolic pathways.
Mol Toxicol
PMID:Metabolism of the tropine indole-3-carboxylate ICS 205-930 by differentiated rat and human hepatoma cells. 285 46

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 which are bordered with microvilli and contain osmiophilic substance. These lumina, demonstrated as intracellular by the Ruthenium red method, in a preceeding paper, seem to originate from modifications of Golgi apparatuses such as dilatation and fusion of the stacks and genesis of microvilli which evaginate from cytoplasmic strands and present filamentous axes related with the network of intermediate filaments surrounding the lumina.
Virchows Arch B Cell Pathol Incl Mol Pathol 1985
PMID:Origin of intracellular lumina in HT 29 colonic adenocarcinoma cell line. An ultrastructural study. 285 87


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