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)

Based upon our previous report indicating the presence of retrovirus-like particles in human gastric cancer cells, we analyzed the putative endogenous reverse transcriptase activity these particles should have. To evaluate the specificity of reverse transcription over that displayed by normal cellular DNA polymerases, the following discriminatory criteria were used: 1) resistance to high concentrations of Actinomycin D; 2) sensitivity to preincubation with ribonuclease A; 3) behavior in cesium sulfate isopycnic gradients and 4) size-shifting of putative template-product complexes after RNase exposure in agarose gel electrophoresis. We report a significant endogenous reverse transcriptase activity associated with membrane-encapsidated particles from terminally-illed patients but not in normal counterparts. Although these structures closely resemble retro viruses, a new model is proposed to explain our findings.
Cell Mol Biol (Noisy-le-grand) 1992 Nov
PMID:Further characterization of RNA-dependent-DNA polymerase activity in human gastric cancer. 128 60

The effect of interleukin 3 (IL-3) on lymphokine-activated killer cell (LAK) generation in splenic lymphocytes was examined in patients with gastric cancer or idiopathic thrombocytopenic purpura (ITP). IL-3 alone did not induce any significant LAK activity from splenic lymphocytes. However, IL-3 addition to the culture with low-dose IL-2 significantly augmented the activity of LAK cells. Spleen cells precultured with IL-3 for 2 days and then added to IL-2 became more potent LAK cells than the spleen cells cultured with the same doses of IL-3 plus IL-2. Phenotypic analysis using flow cytometry demonstrated that IL-2 alone increased in cells expressing CD2+, -11+, and -16+ cells, whereas IL-3 plus IL-2 induced the expansion of CD3+ and CD8+ cells in addition to CD2+, -11+, and -16+ cells. These results suggest that IL-3 plus IL-2 phenotypically induces not only natural killer-like LAK cells (CD2+, -11+, and -16+) but T cell-like LAK cells (CD3+ and -8+). We are now investigating the characteristics of immature T cell populations in the spleen responsive to IL-3 using T-cell receptor antibody.
Mol Biother 1992 Jun
PMID:Augmentation of human lymphokine-activated killer cell activity in splenic lymphocytes by the combination of low-dose interleukin 2 plus interleukin 3. 151 99

Overexpression of the Multiple Drug Resistance gene (MDR1) has been proposed as a major mechanism related to both intrinsic and acquired resistance to chemotherapeutic agents. The gene product is a membrane protein (P-glycoprotein), that acts as an energy-dependent drug efflux pump decreasing drug accumulation in resistant tumor cells. We have characterized MDR1 and P-Glycoprotein expression in human gastric adenocarcinoma and in precursor lesions. MDR1 mRNAs, analyzed by dot-blot technique, were detected in 9 of 10 non-tumoral gastric mucosae and in 8 of 10 gastric adenocarcinomas. Immunohistochemical analysis, using the MRK16 monoclonal antibody, revealed heterogeneous expression of P-Glycoprotein in individual cells. The P-Glycoprotein was found on the surface of cells of gastric areas with intestinal metaplasia subtype III. This type of intestinal metaplasia, also called "colonic metaplasia", has been strongly associated with a high risk for the development of gastric cancer. The fact that the P-Glycoprotein was detected in this precursor lesion is consistent with the intestinal metaplasia-dysplasia and carcinoma sequence proposed in the histogenesis of this tumour. The finding that P-Glycoprotein was heterogeneously expressed in malignant cells of some gastric adenocarcinomas also suggests that this transporter system probably contributes to primary and secondary multidrug resistance in this neoplasm.
Virchows Arch B Cell Pathol Incl Mol Pathol 1991
PMID:Multidrug resistance gene and P-glycoprotein expression in gastric adenocarcinoma and precursor lesions. 167 10

A qualitative analysis of endogenous protein phosphorylation in microsomal fractions from surgical specimens of human gastric cancer, benign gastric ulcers and normal gastric tissues is presented. Fractions were incubated in the presence of (gamma-32P)ATP to measure the transfer of (gamma-32P) to natural substrates mediated by endogenous protein kinases. Phosphoproteins were characterized through PAGE-SDS and detected by autoradiography. KOH at high temperature was used to select for tyrosine-phosphorylated polypeptides on dried gels. We report a notorious enhancement in overall protein phosphorylation in gastric cancer samples over benign ulcers and normal controls as well. Moreover, a highly basic-low molecular weight phosphoprotein is found through 2-D protein gel analysis and a 50 kDa protein is detected only in the presence of Mg2+ after KOH treatment. These two proteins might become putative molecular markers to detect this type of neoplasia.
Cell Mol Biol 1991
PMID:Differential protein phosphorylation in human gastric adenocarcinomas. 180 88

The c-erbB-2 gene is a v-erbB-related proto-oncogene which is distinct from the gene encoding the epidermal growth factor receptor. By using two independent methods, hybridization of both sorted chromosomes and metaphase spreads with cloned c-erbB-2 DNA, we mapped the c-erbB-2 locus on human chromosome 17 at q21, a specific breakpoint observed in a translocation associated with acute promyelocytic leukemia. Furthermore, we observed amplification and elevated expression of the c-erbB-2 gene in the MKN-7 gastric cancer cell line. These data suggest possible involvement of the c-erbB-2 gene in human cancer.
Mol Cell Biol 1986 Mar
PMID:Localization of a novel v-erbB-related gene, c-erbB-2, on human chromosome 17 and its amplification in a gastric cancer cell line. 243 Jan 75

The c-Ha-ras-1 proto-oncogene locus is characterized by a restriction fragment length polymorphism resulting from length variation in a variable tandem repetition (VTR) region downstream from the structural part of the gene. The presence of uncommon alleles at this region has been suggested to be an informative marker for the development of different malignancies, including solid tumours. In order to identify possible genetic markers of cancer risk, we studied the c-Ha-ras-1 locus polymorphism in an Italian population characterized by a high incidence of stomach tumours. Gastric cancer patients, some having first-degree relatives affected by the same malignancy, and control subjects were studied. A total of 176 DNAs was analysed by the Southern blotting technique with TaqI restriction enzyme. This yields a fragment containing the sequence of variable length (VTR) and also allows detection of a cleavage site polymorphism. Thirteen different alleles were detected and some new common and rare variants were found. Our results do not provide evidence that the inheritance of any allele may predispose to gastric malignancies. Segregation analysis carried out on 13 patients' families demonstrated, without exception, a Mendelian inheritance of patterns.
Mol Biol Med 1988 Dec
PMID:Study of the c-Ha-ras-1 locus polymorphism in an Italian population with high incidence of gastric cancer. 290 1

To elucidate the histogenesis of gastric scirrhous cancer, the promotion of collagen production by normal human skin fibroblasts (HSF-1) with human gastric cancer cells (KATO-III, MKN-45 and MKN-28) was investigated by direct coculture and parabiotic culture. Argyrophilic collagenous fibers were demonstrated among fibroblasts on both direct cocultures and parabiotic cultures of the fibroblasts with gastric cancer cells. Microscopic examination showed that these fibers appeared earlier and were more abundant and thicker in direct cocultures and parabiotic cultures than in single cultures of fibroblasts. Gastric cancer cells in single or parabiotic culture did not form argyrophilic fibers. For quantitative proof of the promotion of collagen production by fibroblasts with gastric cancer cells, hydroxyproline produced by fibroblasts was measured. Much higher fibroblast hydroxyproline values were obtained in parabiotic cultures with gastric cancer cell lines than in single cultures of HSF-1. Moreover, the rate of collagen synthesis by HSF-1 was much higher than that of any gastric cancer cell line tested. These results demonstrate that gastric cancer cells enhance collagen production by fibroblasts in vitro. This finding suggests that they may produce a factor promoting fibroblast collagen synthesis and that this may contribute to the formation of stromal collagen in human gastric scirrhous cancer.
Virchows Arch B Cell Pathol Incl Mol Pathol 1984
PMID:Promotion of collagen production by human fibroblasts with gastric cancer cells in vitro. 614 24

The K-sam gene was originally cloned from KATO-III human gastric cancer cells and is identical to the bek or keratinocyte growth factor (KGF) receptor (KGFR) or fibroblast growth factor receptor 2 gene. K-sam generates several variant transcripts by alternative splicing, and the most abundant K-sam transcript in KATO-III cells was cloned as the K-sam-IIC3 cDNA, which has the KGF-binding motif and a short carboxyl terminus lacking a putative phospholipase C-gamma 1 association site, Tyr-769. The K-sam-IIC3 cDNA was distinct from the K-sam-IIC1 cDNA, which was the same as the previously reported KGFR cDNA. The K-sam-IIC1 product contains a long carboxyl terminus with Tyr-769. K-sam-IIC3 showed greater transforming activity in NIH 3T3 cells than did K-sam-IIC1, and in gastric cancer cell lines in general, the level of K-sam-IIC3 mRNA was greater than that of K-sam-IIC1 mRNA. Here we report that the K-sam-IIC3 product was less autophosphorylated than the K-sam-IIC1 product in NIH 3T3 transfectants. K-sam-IIC3-transfected keratinocytes showed a stronger mitogenic response to KGF than did K-sam-IIC1 transfectants. Moreover, K-sam-IIC3-transfected L6 myoblast cells hardly differentiated when cultured in differentiation-inducing medium and growth was not significantly affected, while K-sam-IIC1 transfectants showed a differentiated phenotype with a reduced growth rate. These data indicate the difference in the signal transduction mediated by two KGFR-type K-sam variants generated by alternative splicing which might be involved in certain differentiation and carcinogenesis scenarios.
Mol Cell Biol 1995 Jul
PMID:A truncated K-sam product lacking the distal carboxyl-terminal portion provides a reduced level of autophosphorylation and greater resistance against induction of differentiation. 779 73

Detachment of cell-cell adhesion is indispensable for the first step of invasion and metastasis of cancer. This mechanism is frequently associated with the impairment of either E-cadherin expression or function. However, mechanisms of such abnormalities have not been fully elucidated. In this study, we demonstrated that the function of E-cadherin was completely abolished in the human gastric cancer cell line HSC-39, despite the high expression of E-cadherin, because of mutations in one of the E-cadherin-associated cytoplasmic proteins, beta-catenin. Although immunofluorescence staining of HSC-39 cells by using an anti-E-cadherin antibody (HECD-1) revealed the strong and uniform expression of E-cadherin on the cell surface, cell compaction and cell aggregation were not observed in this cell. Western blotting (immunoblotting) using HECD-1 exhibited a 120-kDa band which is equivalent to normal E-cadherin. Northern (RNA) blotting demonstrated a 4.7-kb band, the same as mature E-cadherin mRNA. Immunoprecipitation of metabolically labeled proteins with HECD-1 revealed three bands corresponding to E-cadherin, alpha-catenin, and gamma-catenin and a 79-kDa band which was apparently smaller than that of normal beta-catenin, indicating truncated beta-catenin. The 79-kDa band was immunologically identified as beta-catenin by using immunoblotting with anti-beta-catenin antibodies. Examination of beta-catenin mRNA by the reverse transcriptase-PCR method revealed a transcript which was shorter than that of normal beta-catenin. The sequencing of PCR product for beta-catenin confirmed deletion in 321 bases from nucleotides +82 to +402. Southern blotting of beta-catenin DNA disclosed mutation at the genomic level. Expression vectors of Beta-catenin were introduced into HSC-39 cells by transfection. In the obtained transfectants, E-cadherin-dependent cell-cell adhesiveness was recovered, as revealed by cell compaction, cell aggregation, and immunoflourescence staining. From these results, it was concluded that in HSC-39 cells, impaired cell-cell adhesion is due to mutations in beta-catenin which results in the dysfunction of E-cadherin.
Mol Cell Biol 1995 Mar
PMID:Loss of E-cadherin-dependent cell-cell adhesion due to mutation of the beta-catenin gene in a human cancer cell line, HSC-39. 786 12

The human bacterial pathogen Helicobacter pylori has been suggested to be the causative agent of the most common chronic infection of man. Since its first isolation in 1982, H. pylori has been associated with gastric and duodenal ulcer disease, and more recently, gastric cancer. The proteolytic digestion of gastric mucus by this microorganism has been suggested as an important mechanism by which its pathogenicity is at least partly exerted. Here we report the detection of protease activity in H. pylori total-cell and supernatant extracts. On the basis that zinc metalloproteases are common microbial pathogenicity factors, we identified a single protein in H. pylori protein extracts with antibodies to the Pseudomonas aeruginosa elastase (a secreted zinc metalloprotease). This same protein was identified by pooled serum from patients infected with H. pylori. We used the functional and immunological relationship between the P. aeruginosa elastase and the Vibrio cholerae haemagglutinin/protease (HAP) to clone the H. pylori hap gene, which was over 99% similar to the V. cholerae hap gene in the coding region. A 4 kb DNA fragment containing the entire cloned gene was highly unstable in Escherichia coli and Bacillus subtilis cloning vectors. We also demonstrated that a hap-like gene sequence is present in all nine Helicobacter species so far discovered. The V. cholerae HAP was first classified on the basis of its mucinase activity.
Mol Microbiol 1994 Jul
PMID:The human gastric pathogen Helicobacter pylori has a gene encoding an enzyme first classified as a mucinase in Vibrio cholerae. 880 63


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