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:3.1.30.2 (endonuclease)
18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chromosome G-banding analysis of two human mammary carcinoma cell lines, Elco and MCF-7, showed the existence of two X chromosomes in both cell lines. To determine the state of activity of the X chromosomes, a methylation-sensitive restriction endonuclease, HpaII, was used to distinguish the active X from the hypermethylated, inactive X chromosome with a probe for the phosphogalactokinase locus by Southern blot hybridization. DNA digested with the restriction enzymes PstI and BstXI showed a band at either 1.05 or 0.9 kilobases. After HpaII digestion, a 50% reduction in intensity was observed in the female controls, whereas total reduction of the band was observed for the tumor cell lines and the male control. This indicates the absence of an inactive X and the presence of only active X chromosomes in the mammary carcinoma cell lines and the male control. To investigate the mechanisms involved in the alteration of the X chromosome composition and activity, restriction fragment length polymorphism analyses of seven additional X chromosome markers (L1.28, DX13, p52A, pX65H7, L782, pA13.RI, and pXG-12) were performed on the DNA isolated from the tumor cells and controls. Heterozygosity for at least one of the seven markers was detected in the six female controls whereas only homozygosity was detected for each marker in the tumor cell lines and the male control. These results indicate that the two active X chromosomes identified in each of the two tumor cell lines are identical, resulting from duplication or nondisjunction of the active X and loss of the inactive X chromosome.
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PMID:Two identical active X chromosomes in human mammary carcinoma cells. 197 Nov 94

California wild mouse-derived ecotropic virus Cas-Br-M induces a spongiform encephalopathy and a wide variety of hematopoietic neoplasms on inoculation of neonatal mice. We isolated a MCF virus [Ns-6(186) MCF] from a thymic T-cell lymphoma developing in a NFS mouse inoculated with Cas-Br-M virus. Biologically cloned NS-6(186) MCF virus, in contrast to previously studied MCF viruses, was found to induce thymic or nonthymic T-cell lymphomas with high efficiency in the absence of ecotropic helper virus. Comparison of the restriction endonuclease maps derived from Cas-Br-M and NS-6(186) MCF revealed differences only in the env region, between 5.8 and 7.8 kb from the 5' end. Two biologically active molecular clones of the NS-6(186) MCF (clone 15 with two LTRs and clone 19 with 1 LTR) were studied. Although both clones exhibited similar in vitro activities, clone 15-derived virus induced only T-cell lymphomas with short latency whereas clone 19-derived virus induced a wide variety of neoplasms with a significantly longer latency. Nucleotide sequence analysis established that the U3 region of each of the two LTRs of clone 15 has a 53-bp duplication which includes "enhancer elements," but that the single LTR of clone 19 has no such duplication.
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PMID:Biologic and molecular genetic characteristics of a unique MCF virus that is highly leukemogenic in ecotropic virus-negative mice. 253 9

A new class of MuLV has been detected and isolated from normal and leukemic AKR, C58, SJL, and NFS.AKV mice as well as from NFS mice inoculated with Friend or Moloney ecotropic viruses. These new viruses are XC negative and serologically cross-react with MCF env antigens but are ecotropic in host range, being able to only infect mouse cells to varying degrees and unable to infect mink or other cells infectable by MCF or xenotropic viruses. Viruses of this type from AKR mice cross-interfere with Moloney ecotropic and MCF viruses in SC-1 cells and appear to have properties similar to those of the SL3-2, GPA-V2, and R-XC- isolates. Analysis of their genomes by restriction endonuclease mapping of proviral DNA indicates structures similar to class II MCFs with the 5' half of the genome being like ecotropic viruses and the env region exhibiting restriction sites characteristic of MCF viruses. In normal AKR mice, these ecotropic recombinant-like viruses are found in spleen and bone marrow as early as 1 week of age, but first appear in the thymus at 3-4 months of age. These viruses have not been detected in mice with no or low expression of ecotropic viruses (NFS, NZB, DBA/2, BALB/c, C57BL/6). Because of their apparent recombinant structure and ecotropic host range we have provisionally designated them ecotropic recombinant virus (ERV) to distinguish them from the MCF class of recombinant MuLV.
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PMID:A new class of retrovirus present in many murine leukemia systems. 300 31

Molecular clones of closed circular DNA molecules of a mink cell focus-inducing murine leukemia virus (MCF-13 MuLV) were generated. Closed circular DNA molecules isolated from a Hirt extraction of recently infected NIH/3T3 cells were inserted at their unique EcoRI site into lambda gtWES.lambda B. Restriction endonuclease analysis of inserts of two clones indicated that they represented intact MCF-13 MuLV genomes. One viral insert contained two large terminal repeat sequences, and the other contained only one. A 300-base-pair DNA fragment located in the envelope region of the MCF-13 MuLV genome was determined to be related to xenotropic MuLV sequences.
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PMID:Identification of a DNA fragment from a molecularly cloned mink cell focus-inducing murine leukemia virus specific for xenotropic virus-related sequences. 628 10

To date, apoptosis has been characterized biochemically by the production of 180-200 bp internucleosomal DNA fragments resulting from the activation of an endonuclease(s). The principal morphological feature of apoptosis is the condensation of chromatin and it has been assumed that this may reflect the oligonucleosomal fragmentation pattern. We have re-examined this dogma by comparing the biochemical and morphological features of cell death in several epithelial cell types (HT-29-I1 colon adenocarcinoma, CC164 mink lung, DU-145 human prostatic carcinoma and MCF-7 human breast adenocarcinoma) and one mesenchymal cell line (H11ras-R3 ras-transformed rat fibroblasts). Cell death was induced either by serum deprivation, TGF-beta 1 or etoposide, or by leaving cells to reach confluence. Cell death was assessed with respect to detachment from monolayers, morphological changes and DNA integrity. The DNA-binding fluorophore Hoechst 33258 revealed chromatin condensation patterns consistent with apoptotic cell death in all cell types except MCF-7 cells. Using field inversion gel electrophoresis in conjunction with conventional 2% agarose gel electrophoresis, cleavage of DNA to 50 kbp fragments was observed in all cases except MCF-7 cells. This preceded the appearance of oligonucleosomal fragments in HT-29-I1, CC164 and H11ras-R3 cells. Although the DNA of DU-145 cells fragmented into 50 kbp units, and although the cells exhibited classical apoptotic morphology, no subsequent internucleosomal cleavage was observed. These results suggest that changes in the integrity of DNA indicative of the release of chromatin loop domains occur before cleavage at internucleosomal sites is initiated and that the latter is not an essential step in the apoptotic process.
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PMID:Apoptotic death in epithelial cells: cleavage of DNA to 300 and/or 50 kb fragments prior to or in the absence of internucleosomal fragmentation. 825 89

The induction of cell death along with cell-cycle arrest is one of the foremost mechanisms regulating cell growth. In the human breast carcinoma cell line MCF-7 we investigated two chemotherapeutic agents, the antiestrogen tamoxifen and the DNA-damaging drug cisplatin, for the relative contribution of these mechanisms to growth inhibition in culture. Growth kinetics and flow cytometry confirmed that tamoxifen at 1 microM acts mainly by arresting cells in the G0/G1 phase of the cell cycle. Compared to untreated controls, only a few more cells were detached from the monolayer and dead after a 5-day incubation. On the other hand, cisplatin at 1 microM did not induce the well-defined G2/M-arrest reported for other cell types, but resulted in a marked increase in the rate of cell death. A morphological feature observed, especially with cisplatin-treated MCF-7 cells, was the formation of numerous micronuclei (in up to 30% of the cells) and an increase in the number of binucleate cells (up to 20%). In both tamoxifen- and cisplatin- treated cultures, cell death appeared to occur by apoptosis, as indicated morphologically by cellular and nuclear shrinkage accompanied by DNA-condensation and ultimately the formation of DNA containing apoptotic bodies. However, no internucleosomal DNA degradation or endogenous endonuclease activity could be detected in the cells of the monolayer or in the mainly dead and detached cells of the culture supernatant. DNA fragmentation was only observed when isolated MCF-7 nuclei were incubated with exogenous endonucleases. However, as determined by reverse transcriptase/polymerase chain reaction amplification, MCF-7 cells do express the mRNA for DNase I, an endonuclease known to be involved in apoptosis. Thus, apoptosis is part of the growth-inhibitory process and occurs without apparent internucleosomal DNA fragmentation in MCF-7 cell cultures.
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PMID:Cell-cycle arrest, micronucleus formation, and cell death in growth inhibition of MCF-7 breast cancer cells by tamoxifen and cisplatin. 887 58

The identification of genes whose expression is altered following exposure to a low dose of ionizing radiation (IR) is an important step in understanding the phenomenon of the adaptive response. Using the differential mRNA display method we have identified a gene whose expression is up-regulated following exposure to 0.25 Gy IR. Partial DNA sequence and restriction endonuclease analysis of this gene showed that it is identical to the gene encoding for the human peptide-binding protein 74 (PBP74/mortalin/Grp75), a member of the heat shock 70 protein family. Time-course measurement of the PBP74/mortalin/Grp75 mRNA showed that its level was elevated after a lag of at least 15 min. The maximum induction appears to be at 30 min following gamma-irradiation and there is then a steady decline to control levels within 5 h in the HT29 cell line. On the other hand, the level of the PBP74/mortalin/Grp75 mRNA in the human breast adenocarcinoma cell line MCF-7 is consistently elevated after gamma-irradiation for up to 6 h post-irradiation. Furthermore, a cell line that does not demonstrate the induced radioresistance phenomenon (SW48) shows no induction of the PBP74/mortalin/Grp75 mRNA in contrast with HT29 or MCF-7. Treatment of the HT29 cells with antisense oligonucleotide directed towards the initiation codon of PBP74 sensitized cells to ionizing radiation.
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PMID:Induction of PBP74/mortalin/Grp75, a member of the hsp70 family, by low doses of ionizing radiation: a possible role in induced radioresistance. 941 87

Somatostatin (SST) analogs inhibit tumor cell growth by exerting direct anti-proliferative effects with cytostatic (growth arrest) or cytotoxic (apoptosis) consequences. The SST analog SMS 201-995 (octreotide, OCT) inhibits growth of MCF-7 human breast adenocarcinoma cells, which express multiple SSTRs. Its action has been reported to result in either apoptosis or growth arrest, but the underlying mechanisms have not been elucidated in this tumor cell model. Here, we report that OCT elicits cytotoxic response in these cells, leading to apoptosis, which is associated with a rapid, time-dependent induction of wild-type p53 and an increase in Bax. There was no G1 cell-cycle arrest in these cells during OCT treatment as suggested by the decrease in G1/S ratio and the lack of induction of pRb and p21. Additionally, we demonstrate that OCT-induced DNA fragmentation in this cell line is due to selective activation of a cation-insensitive acidic endonuclease. Our data provide a rationale for utilizing SST analogs to treat SSTR-positive breast cancer cells expressing wild-type p53.
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PMID:Induction of wild-type p53, Bax, and acidic endonuclease during somatostatin-signaled apoptosis in MCF-7 human breast cancer cells. 953 89

The G protein-coupled receptor agonist somatostatin (SST)-induces apoptosis in MCF-7 human breast cancer cells. This is associated with induction of wild-type p53, Bax, and an acidic endonuclease. We have shown recently that its cytotoxic signaling is mediated via membrane-associated SHP-1 and is dependent on decrease in intracellular pH (pHi) to 6.5. Here we investigated the relationship between intracellular acidification and SHP-1 in cytotoxic signaling. Clamping of pHi at 7.25 by the proton-ionophore nigericin abolished SST-signaled apoptosis without affecting its ability to regulate SHP-1, p53, and Bax. Apoptosis could be induced by nigericin clamping of pHi to 6.5. Such acidification-induced apoptosis was not observed at pHi <6.0 or >6.7. pHi-dependent apoptosis was associated with the translocation of SHP-1 to the membrane, enhanced in cells overexpressing SHP-1, and was abolished by its inactive mutant SHP-1C455S. Acidification caused by inhibition of Na+/H+ exchanger and H+ ATPase (pHi = 6.55 and 6.65, respectively) also triggered apoptosis. The effect of concurrent inhibition of Na+/H+ exchanger and H(+)-ATPase on pHi and apoptosis was comparable with that of SST. Acidification-induced, SHP-1-dependent apoptosis occurred in breast cancer cell lines in which SST was cytotoxic (MCF-7 and T47D) or not (MDA-MB-231). We conclude that: (a) SST-induced SHP-1-dependent acidification occurs subsequent to or independent of the induction of p53 and Bax; (b) SST-induced intracellular acidification may arise due to inhibition of Na+/H+ exchanger and H(+)-ATPase; and (c) SHP-1 is necessary not only for agonist-induced acidification but also for the execution of acidification-dependent apoptosis. We suggest that combined targeting of SHP-1 and intracellular acidification may lead to a novel strategy of anticancer therapy bypassing the need for receptor-mediated signaling.
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PMID:Interdependent regulation of intracellular acidification and SHP-1 in apoptosis. 1019 42

Diverse classes of phytochemicals initiate biological responses that effectively lower cancer risk. One class of phytochemicals, broadly defined as pure and mixed isoprenoids, encompasses an estimated 22,000 individual components. A representative mixed isoprenoid, gamma-tocotrienol, suppresses the growth of murine B16(F10) melanoma cells, and with greater potency, the growth of human breast adenocarcinoma (MCF-7) and human leukemic (HL-60) cells. beta-Ionone, a pure isoprenoid, suppresses the growth of B16 cells and with greater potency, the growth of MCF-7, HL-60 and human colon adenocarcinoma (Caco-2) cells. Results obtained with diverse cell lines differing in ras and p53 status showed that the isoprenoid-mediated suppression of growth is independent of mutated ras and p53 functions. beta-Ionone suppressed the growth of human colon fibroblasts (CCD-18Co) but only when present at three-fold the concentration required to suppress the growth of Caco-2 cells. The isoprenoids initiated apoptosis and, concomitantly arrested cells in the G1 phase of the cell cycle. Both suppress 3-hydroxy-3-methylglutaryl CoA reductase activity. beta-Ionone and lovastatin interfered with the posttranslational processing of lamin B, an activity essential to assembly of daughter nuclei. This interference, we postulate, renders neosynthesized DNA available to the endonuclease activities leading to apoptotic cell death. Lovastatin-imposed mevalonate starvation suppressed the glycosylation and translocation of growth factor receptors to the cell surface. As a consequence, cells were arrested in the G1 phase of the cell cycle. This rationale may apply to the isoprenoid-mediated G1-phase arrest of tumor cells. The additive and potentially synergistic actions of these isoprenoids in the suppression of tumor cell proliferation and initiation of apoptosis coupled with the mass action of the diverse isoprenoid constituents of plant products may explain, in part, the impact of fruit, vegetable and grain consumption on cancer risk.
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PMID:Apoptosis and cell-cycle arrest in human and murine tumor cells are initiated by isoprenoids. 1020 54


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