Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.23 (beta-galactosidase)
14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An androgen-repressed human prostate cancer cell line, ARCaP, was established and characterized. This cell line was derived from the ascites fluid of a patient with advanced metastatic disease. In contrast to the behavior of androgen-dependent LNCaP and its androgen-independent C4-2 subline, androgen and estrogen suppress the growth of ARCaP cells in a dose-dependent manner in vivo and in vitro. ARCaP is tumorigenic and highly metastatic. It metastasizes to the lymph node, lung, pancreas, liver, kidney, and bone, and forms ascites fluid in athymic hosts. ARCaP cells express low levels of androgen receptor mRNA and prostate-specific antigen mRNA and protein. Immunohistochemical staining shows that ARCaP cells stain intensely for epidermal growth factor receptor, c-erb B2/neu, and c-erb B3. Staining is negative for chromogranin A and positive for bombesin, serotonin, neuron-specific enolase, and the c-met protooncogene (a hepatic growth factor/scatter factor receptor). ARCaP cells also secrete high levels of gelatinase A and B and some stromelysin, which suggests that this cell line may contain markers representing invasive adenocarcinoma with selective neuronendocrine phenotypes. Along with its repression of growth, androgen is also found to repress the expression of prostate-specific antigen in ARCaP cells as detected by a prostate-specific antigen promoter-beta-galactosidase reporter assay. Our results suggest that the androgen-repressed state may be central to prostate cancer progression and that advanced prostate cancer can progress from an androgen-independent to an androgen-repressed state.
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PMID:Androgen-repressed phenotype in human prostate cancer. 898 79

We evaluated the efficiency of gene transduction and of gene expression by adenoviral vectors in human lung adenocarcinoma cells. Freshly isolated cancer cells were collected from pleural effusions in adenocarcinoma patients by centrifugation with a Percoll gradient. Adenoviral vectors resulted in effective gene transduction into human lung cancer cell lines and into freshly isolated lung adenocarcinoma cells. In an experiment using the beta-galactosidase (LacZ) gene, the Adex1CA vector with a regulatory sequence of chicken beta-actin as promoter and an enhancer derived from cytomegalovirus produced a higher transduction ratio and greater expression levels than adenoviral vectors with other promoter systems. Transduction with Adex1CA vectors containing the human interleukin-2 (IL-2) gene (Adex1CAhIL-2) resulted in enhanced secretion of IL-2 from gene-modified lung cancer cells. Treatment with normal human serum inhibited gene transduction by Adex1CAhIL-2 but did not inhibit gene expression after transduction by Adex1CAhIL-2. The secretion of IL-2 from the gene-modified cells, which were irradiated at 100 Gy before transduction, continued for 8 days. In a mouse model, the intrapleural injection of IL-2 gene-modified 3LL cells transduced by Adex1CAhIL-2 could cure the pre-existing lung tumours with malignant pleural effusions to induce tumor-specific immunity. But these therapies did not show any therapeutic benefit on the pre-existing tumor in subcutaneous region. These data suggest a potentially useful but limited clinical role of Adex1CAhIL-2 in gene therapy for lung cancer patients.
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PMID:Interleukin-2 gene transduction into freshly isolated lung adenocarcinoma cells with adenoviral vectors. 898 90

Modified vaccinia virus Ankara (MVA), a highly attenuated strain of vaccinia virus (VV) that is unable to replicate in most mammalian cells, was evaluated as an expression vector for a model tumor associated antigen (TAA) and as a potential anti-cancer vaccine. We employed an experimental murine model in which an adenocarcinoma tumor line, CT26.CL25, was stably transfected with a model TAA, beta-galactosidase (beta-gal). Mice injected intramuscularly with a recombinant MVA (rMVA) expressing beta-gal (MVA-LZ), were protected from a lethal intravenous (i.v.) challenge with CT26.CL25. In addition, splenocytes from mice primed with MVA-LZ were therapeutically effective upon adoptive transfer to mice bearing pulmonary metastases of the CT26.CL25 tumor established 3 days earlier. Most importantly, i.v. inoculation with MVA-LZ resulted in significantly prolonged survival of mice bearing three day old pulmonary metastases. This prolonged survival compared favorably to mice treated with a replication competent recombinant VV expressing beta-gal. These findings indicate that rMVA is an efficacious alternative to the more commonly used replication competent VV for the development of new recombinant anti-cancer vaccines.
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PMID:Highly attenuated modified vaccinia virus Ankara (MVA) as an effective recombinant vector: a murine tumor model. 914 Dec 9

The herpes simplex thymidine kinase (HStk) gene induces regression of epithelial tumors after ganciclovir (GCV) administration. This observation has been attributed to both gene transfer and metabolic cooperation between cells (the bystander effect). This study evaluates the relative roles of the bystander effect and gene delivery of the HStk gene by the LTKOSN.2 vector. MC38 colon adenocarcinoma cells, syngeneic for C57/B16 mice, were used. Whereas in vitro proliferation assays demonstrated a bystander effect, significantly greater inhibition of proliferation occurred with HStk gene transfer. In mixtures containing 75 per cent MC38 cells with no vector (MC38 NV) and 25 per cent MC38 pretransduced with LTKOSN.2 (MC38 TK), proliferation was inhibited by 62 +/- 5 per cent. In mixtures containing 75 per cent MC38 NV with 25 per cent HStk vector-producing cells (LTKOSN.2 VPC), proliferation was inhibited by 97 +/- 1 per cent. In vivo subcutaneous mixture experiments utilized MC38 NV cells inoculated at a 1:1 ratio with various treatment cell groups followed by administration of GCV. Tumor volumes (mean +/- standard error) at 30 days were: 264 +/- 66 mm3 for MC38 TK, 0 for LTKOSN.2 VPC, 1009 +/- 335 mm3 for lacZ VPC (beta-galactosidase VPC), and 1012 +/- 212 mm3 for NIH3T3 (nontransduced cells). These data suggest that in vivo, the bystander effect alone causes tumor inhibition, but gene transfer is necessary for complete tumor elimination in immunocompetent mice.
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PMID:Herpes simplex thymidine kinase gene transfer is required for complete regression of murine colon adenocarcinoma. 920 36

Telomerase is active in germline cells and tumor cells, but is either not expressed or is repressed in a majority of somatic cells. The regulation mechanism of telomerase activity has lately drawn considerable attention for the possible use of telomerase inhibitors for anti-cancer therapy. We analyzed the regulation mechanism of telomerase activity in the human lung adenocarcinoma cell line A549 and its subline A5DC7 which shows impaired tumor phenotypes. Although A549 and A5DC7 cells have similar growth potentials, when cultured in medium supplemented with 5% fetal bovine serum A5DC7 cells demonstrated a remarkable negative regulation of telomerase activity and telomere shortening. After the long-term culture, A5DC7 cells showed a large senescent cell-like morphology, arrested growth at the 106 population doubling level and entered senescence which was demonstrated by expression of the beta-galactosidase senescence marker. When the serum concentration was raised from 5% to 10% for the senescent A5DC7 cells, telomerase reactivation and telomere lengthening occurred as well as resumption of proliferation. These results demonstrate that the growth arrest seen in senescent A5DC7 cells is reversible and that telomerase activity is also bi-directionally regulated in A5DC7 cells, an event which could not be observed in normal senescent cells. This indicates that stringent telomerase repression and complete growth arrest concomitant with cellular senescence is collapsed in senescent A5DC7 cells in response to exogenous signals. Our study suggests that cellular senescence progresses and/or is regulated at multiple levels.
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PMID:Bidirectional regulation of telomerase activity in a subline derived from human lung adenocarcinoma. 926 7

Sindbis virus, the prototype alphavirus, kills cells by inducing apoptosis. To investigate potential mechanisms by which Sindbis virus induces apoptosis, we examined whether specific viral gene products were able to induce cell death. Genes encoding the three structural proteins--capsid, the precursor E1 (6K plus E1), and the precursor E2 (P62 or E3 plus E2)--were cotransfected with a beta-galactosidase reporter plasmid in transient-transfection assays in rat prostate adenocarcinoma AT3 cells. Cell death, as determined by measuring the loss of blue cells, was observed in AT3 cells transfected with 6K plus E1 and with P62 but not in cells transfected with capsid. Deletion mutagenesis of P62 indicated that large regions of the cytoplasmic domain and extracellular domain were not essential for the induction of cell death. However, constructs containing the minimal E3 signal sequence fused to the E2 transmembrane domain and the minimal E3 signal sequence fused to the E1 transmembrane domain induced death as efficiently as full-length P62 and 6K plus E1, whereas no cell death was observed after transfection with a control construct containing the E3 signal sequence linked to the transmembrane domain of murine CD4. These data demonstrate that intracellular expression of the transmembrane domains of the Sindbis virus envelope glycoproteins can kill AT3 cells.
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PMID:The transmembrane domains of Sindbis virus envelope glycoproteins induce cell death. 955 79

We hypothesized that viral mediated transfer of Na+,K+-ATPase subunit genes to alveolar epithelial cells to overexpress Na+, K+-ATPase could increase Na+,K+-ATPase function. We produced replication-deficient human type 5 adenoviruses that contained cytomegalovirus (CMV)-driven cDNAs for the rat alpha1 and beta1 subunits of Na+,K+-ATPase (AdMRCMValpha1 and AdMRCMVbeta1, respectively). These viruses were used to transduce human adenocarcinoma cells (A549) in culture. Na+,K+-ATPase function was increased by 2.5-fold in the AdMRCMValpha1-infected cells. Sham and AdMRCMVbeta1-infected cells, and cells infected by a CMV-driven beta-galactosidase-expressing adenovirus, had no increases in Na+, K+-ATPase activity. A549 cells infected with multiplicities of infection of 10-200 of AdMRCMValpha1 demonstrated expression of a rat alpha1 mRNA and increased alpha1 protein; no change in beta1 message or protein was noted. Ouabain sensitivity was measured in A549 cells following infection with AdMRCMValpha1. In contrast to controls, AdMRCMValpha1-infected cells demonstrated two IC50s. The first was similar to the IC50s of the controls; the second IC50 was 2 logs greater than the first, consistent with the presence of both the rat and human alpha1 isozymes. These results demonstrate for the first time that adenoviruses can be used to augment Na+,K+-ATPase function.
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PMID:Overexpression of the Na+,K+-ATPase alpha1 subunit increases Na+,K+-ATPase function in A549 cells. 961 78

Animal in vivo studies and human epidemiological observations indicated potent anticancer effects for tea. Here we demonstrate that epigallocatechin gallate (EGCG), a major tea catechin, strongly and directly inhibits telomerase, an enzyme essential for unlocking the proliferative capacity of cancer cells by maintaining the tips of their chromosomes. Telomerase inhibition was elaborated in a cell-free system (cell extract) as well as in living cells. In addition, the continued growth of two representative human cancer cell lines, U937 monoblastoid leukemia cells and HT29 colon adenocarcinoma cells, in the presence of nontoxic concentrations of EGCG showed life span limitations accompanied with telomere shortening, chromosomal abnormalities, and expression of the senescence-associated beta-galactosidase. It is suggested that telomerase inhibition could be one of the major mechanisms underlying the anticancer effects of tea.
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PMID:Telomerase inhibition, telomere shortening, and senescence of cancer cells by tea catechins. 971 7

Cellular nuclease activity is a potential barrier to the successful delivery of foreign genes to mammalian cells. We tested the hypothesis that transfection in the presence of a specific DNase inhibitor can enhance the expression of foreign gene products. We have used DMI-2, a polyketide metabolite of Streptomyces sp. strain 560 to enhance the expression of bacterial chloramphenicol acetyltransferase (CAT) in the human lung adenocarcinoma cell line H441. DMI-2 has been shown previously to inhibit porcine DNase II, an acid pH nuclease contained in the endosomal/lysosomal compartment. Transfection of H441 cells in the presence of 0.1-1 microgram/ml DMI-2 caused: (1) 10-fold enhancement of CAT activity when the bacterial plasmid was complexed with either surfactant protein A-poly-lysine or transferrin-poly-lysine; (2) 1.5- to two-fold enhancement of CAT activity in cells exposed to lipofectin-DNA complexes: (3) no effect on transfection via calcium phosphate co-precipitation. DMI-2 alone showed no inherent transfection activity. In experiments using SP-A-poly-lysine and plasmid containing the beta-galactosidase reporter gene, DMI-2 increased the number of transfected cells. Methanolysis products of DMI-2 did not inhibit DNase II and did not enhance transfection efficiency. Taken together, the data support the hypothesis that nuclease action is a significant barrier to expression of foreign genes and inhibition of specific nucleases may facilitate transfection.
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PMID:Enhanced reporter gene expression in cells transfected in the presence of DMI-2, an acid nuclease inhibitor. 993 Mar 26

Transforming growth factor-beta (TGF-beta)TG has been shown to play a multifunctional role in tumorigenesis. Here we demonstrate that TGF-beta induces a morphological change and expression of senescence-associated beta-galactosidase activity in the human lung adenocarcinoma cell line A549 cells within a week after the addition. These TGF-beta induced phenotypic changes are thought to characterize the rapid onset of senescence. When A549 cells were treated with TGF-beta, cell growth was not completely arrested, but the activity of telomerase was down regulated via transcriptional repression of telomerase reverse transcriptase, which led to a shortening of the telomere during long-term culture and finally resulted in replicative senescence. These results indicate that TGF-beta is able to induce a rapid senescence in A549 cells without significantly inhibiting cell growth and can further direct A549 cells to a replicative senescence state via the suppression of telomerase which culminates in telomere shortening. All these experimental results suggest that TGF-beta transmits several separate and independent signals to shift A549 cells back to a normal senescent cell.
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PMID:Transforming growth factor beta triggers two independent-senescence programs in cancer cells. 1008 64


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