Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: HUMANGGP:040116 (histone)
 44,835 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dimethylbenzanthracene-induced rat carcinomas possess activities binding cyclic adenosine 3':5'-monophosphate (cAMP) and estrogen. When dimethylbenzanthracene-induced tumors regress after ovariectomy of the host, a change in the specific binding of cAMP and estrogen occurs in the tumors. Six days after ovariectomy, cAMP binding increases 5-fold in the nuclei and 2-fold in the cytosol of tumors, while nuclear and cytoplasmic estrogen binding decreases by 80% and 50%, respectively. These changes in activities binding cAMP and estrogen are detectable within 1 day after ovariectomy and the changes are reversed when resumption of tumor growth is induced by the injection of 17beta-estradiol. When dimethylbenzanthracene-induced tumors fail to regress after ovariectomy, the change in activities binding cAMP and estrogen does not occur. Significant increases in the cAMP level as well as in adenylate cyclase and cAMP-phosphodiesterase activities are also found in the regressing tumors. Concomitant with the increase of cAMP-binding activity is an increase in histone kinase activity in the regressing tumor. These data suggest the involvement of cAMP in the growth control of a hormone-dependent mammary rumor.
 ...
PMID:Cyclic AMP-binding proteins: inverse relationship with estrogen-receptors in hormone-dependent mammary tumor regression. 20 18

During the growth arrest of 7,12-dimethylbenz(alpha) anthracene-induced rat mammary carcinomas following ovariectomy or N6, O2'-dibutyryl cyclic adenosine 3':5'-monophosphate (DBcAMP) treatment, a change in the specific estrogen and cAMP binding to tumor proteins is observed. Three days after ovariectomy or DBcAMP treatment of the hosts, cAMP binding increases 5- and 2-fold in the nuclei and cytosol of tumors, respectively, whereas nuclear and cytoplasmic estrogen binding decreases by 70 and 25%, respectively. These changes in cAMP- and estrogen-binding activities are detectable within 1 day after ovariectomy or DBcAMP treatment, and the changes are reversed when resumption of tumor growth is induced by the injection of estradiol valerate or cessation of DBcAMP treatment. When 7,12-dimethylbenz(alpha)anthracene-induced tumors fail to regress after ovariectomy or DBcAMP treatment, the change in estrogen and cAMP binding does not occur. Concomitant with the increase of cAMP-binding activity in regressing tumors are increases in histone kinase activity and the cAMP content of the tumors. These increases in cAMP-binding and protein kinase activities are blocked by cycloheximide. These data suggest an interaction between a steroid hormone and cAMP in the growth control of a hormone-dependent mammary tumor.
 ...
PMID:Inverse relation between estrogen receptors and cyclic adenosine 3':5'-monophosphate-binding proteins in hormone-dependent mammary tumor regression due to dibutyryl cyclic adenosine 3':5'-monophosphate treatment or ovariectomy. 21 Sep 38

N-Mustard depresses the acetylation of histones in Ehrlich ascites and Walker carcinoma cells. It is demonstrated that this effect is not caused by an accelerated deacetylation but is due to an inhibition of the acetyl-transferase reaction. Employing 4-sulphonatoethylthio-cyclophosphamide it is demonstrated that the alkylating agent affects predominantly the acetylation of a chromatin fraction which is soluble in 0.1M NaCl after digestion with micrococcal nuclease. After removal of the alkylating agent, the recovery of histone acetylation is relatively slow and--in contrast to the repair of DNA cross-links--characterized by a 4-hr lag period. The reduction of histone acetylation by N-mustard is much less expressed in cells which are resistant to the drug than in the sensitive parental lines. This is in contrast to DNA-interstrand cross-links in Walker cells where both N-mustard sensitive and resistant cells inhibit the same cross-link frequency and identical repair rates. Based on these data it is concluded that the inhibition of histone acetylation may be an important part of the mechanism by which alkylating agents inhibit tumor growth.
 ...
PMID:Alkylating antitumor agents reduce histone acetyl-transferase activity. 364 97

The specific activity (dpm/mg protein) of the acid-soluble nuclear material extracted from spleens or lymph nodes (but not other tissues) of tumor-bearing BALB/c mice was approximately twice that of the corresponding tissues from tumor-free mice of the same age and sex following i.p. injection of L-[U-14C]lysine. Autoradiography of gel electrophoretograms showed the major increases in radioactivity to be in histone H2A and histone H2B. Rabbit anti-mouse lymphocyte serum could prevent the splenic response to tumor only if the serum was given at the time of, or very soon after, the tumor transplant. Immunization with sheep red blood cells or with bovine serum albumin in adjuvant did cause an increase in specific activity of the splenic acid-soluble nuclear material, but there was little difference between samples from normal and tumor-bearing mice when the nuclei were purified before extraction. Use of adjuvant, with or without antigen, prevented the tumor-induced increase in the specific activity of the acid-soluble, histone fraction. Thus, adjuvant-induced suppressor cells were able to interfere with lysine incorporation. It was concluded that the tumor must grow within the host for this manifestation, since mice which were immune to the tumor as a result of vaccination had no increase in lysine incorporation, compared to normal, untreated mice. However, vaccinated mice which did not develop immunity had tumor growth and the associated increased splenic histone synthesis. A regulatory role is suggested for the histones H2A and H2B.
 ...
PMID:Increased synthesis of acid-soluble nuclear material in spleens of tumor-bearing BALB/c mice. 392 Dec 40

An a posteriori proposal is made that cancer represents an alien non-body phenotype erupting from "silent" gene groups within actively coding regions of a normal cell's genome. Relevant empirical data is garnered from the literature and twelve premises are derived from the data. On the basis of these premises it is hypothesized that the malignant neoplastic phenotype results from interference with non-histone chromosomal proteins causing retention and expression in a body cell of non-body introns. These are asserted to be the same introns which, as exons in a trophoblast cell, direct the normal development of the fetal placenta. Development of a malignant tumor is presented as a pathological recapitulation of the development of a normal placenta. Unrestrained tumor growth is attributed to the inability of endogenous body chalones to suppress the non-body gene groups coding for neoplastic mitosis, while invasion and metastasis result from failure of the non-body genes which code for implantation and mitosis to switch off at the proper time. The hypothesis asserts that all carcinogenic agents alter phosphorylation of non-histone chromosomal proteins, that cancer and normal trophoblast cells are genetically programmed to travel through the body's vascular system to effect immunosuppression in lymphoid tissues, that malignant neoplastic tissue will regress when exposed to trophoblast-based chalones, and that mammals immunized against trophoblast-based antigen will be resistant to the development of malignant tumors.
 ...
PMID:A proposed model of cancer as the inappropriate expression of non-body introns. 622 Jan 82

The antitumor effect of three structurally closely related alkylating hexitol derivatives (DBD, DAG, DiacDAG) was evaluated using a complex multi-parameter evaluation system. It comprised toxicology, action on ascites and solid tumors, as well as on subpopulations isolated by isopyknic centrifugation, cross-resistance and their action on chromatin components (DNA, histone, nonhistone proteins). The results indicate that in spite of their same mode of action, considerable differences could be observed in tumor specificity, inhibition of tumor growth and in their interaction with chromatin components. This multiparameter system seems to be very useful for comparative studies of other alkylating agents, especially for the evaluation of the effect of chemically closely related compounds.
 ...
PMID:Complex evaluation of the effect of some cytostatic hexitol derivatives. 745 97

Cells expressing the herpes simplex-thymidine kinase (HS-TK) gene as a consequence of retroviral transduction, as well as TK-negative (TK-) bystander cells, can be killed by treatment with ganciclovir (GCV). In vitro, this "bystander effect," has been attributed to metabolic cooperation through gap junctions or to the uptake of apoptotic vesicles. We show that GCV treatment kills TK-negative U-87 glioma cells cocultured with cells that express TK (TK+) but that have lost the capacity for releasing retroviral particles. A photometric enzyme immunoassay identifies histone-associated DNA fragments, typical of apoptosis, in the cytosol of GCV-treated TK+ cells, and apoptotic features are also demonstrated by ultrastructural studies. Northern blot analysis and the reverse transcription polymerase chain reaction (PCR) show that connexin 43, a major constituent of gap junctions, is expressed in TK+ and U-87 cells. The size of U-87 tumors in nude mice subsequently injected with TK+ cells and GCV is not significantly different than in untreated animals; whereas, after injecting 1:1 mixtures of U-87 and TK+ cells, GCV treatment only causes a temporary regression of tumor growth. On the contrary, when the injected mixtures contain PA317.STK.SBA (a retroviral producer cell line that can transduce efficiently the HS-TK gene) and U-87 cells, tumors are destroyed effectively by GCV treatment. Thus, an experimental setting in which U-87 gliomas are matched with cells that are able to express, but not to transduce, the HS-TK gene indicates that the bystander effect kills U-87 cells in vitro by mechanisms associated with apoptotic death. In vivo, this effect is not sufficient to restrain the tumor growth taking place in immunodeficient animals.
 ...
PMID:The "bystander effect": association of U-87 cell death with ganciclovir-mediated apoptosis of nearby cells and lack of effect in athymic mice. 754 76

Polyamines stimulate expression of a variety of genes, including many implicated in cell proliferation. Indeed, aberrant expression of ornithine decarboxylase (ODC), a rate-limiting enzyme in polyamine biosynthesis, plays a causal role in tumorigenesis. Gene activity is influenced by dynamic changes in acetylation of nucleosomal histones. Although polyamines influence the histone acetyltransferase and deacetylase activities in cell-free systems, their ability to modulate these enzymes in live cells has never been established. To examine the effects of elevated intracellular levels of ODC and polyamines on gene transcription and histone acetylation, cells were infected with a retrovirus containing a cDNA for ODC. ODC overexpression potentiated the stimulatory effects of histone deacetylase inhibitors on reporter gene expression beyond that promoted by ODC or inhibitor treatment alone. Indeed, elevated intracellular levels of ODC promoted hyperacetylation of histones in several epidermal and fibroblast cell types. The ODC-mediated increase in acetylated histones was abrogated when cells were treated with alpha-difluoromethylornithine, a specific inhibitor of ODC activity, implying a distinct role for polyamines. Specifically, polyamines were found to enhance the action of histone acetyltransferases either directly or indirectly. Our studies document effects of elevated intracellular polyamine levels on histone acetylation in proliferating cells, suggesting a mechanism by which altered polyamine biosynthesis contributes to aberrant expression of genes, facilitating tumor growth. In addition, these studies may have implications for the development of drugs designed to regulate enzymes that modify the acetylation status of histones.
 ...
PMID:High levels of intracellular polyamines promote histone acetyltransferase activity resulting in chromatin hyperacetylation. 1076 Sep 44

Histone deacetylases (HDACs) catalyze the removal of acetyl groups on the amino-terminal lysine residues of core nucleosomal histones. This activity is associated generally with transcriptional repression. We have reported previously that inhibition of HDAC activity by hydroxamic acid-based hybrid polar compounds, such as suberoylanilide hydroxamic acid (SAHA), induces differentiation and/or apoptosis of transformed cells in vitro and inhibits tumor growth in vivo. SAHA is a potentially new therapeutic approach to cancer treatment and is in Phase I clinical trials. In several tumor cell lines examined, HDAC inhibitors alter the expression of less than 1% of expressed genes, including the cell cycle kinase inhibitor p21(WAF1). In T24 bladder carcinoma cells, SAHA induces up to a 9-fold increase in p21(WAF1) mRNA and protein, which is, at least in part, because of an increase in the rate of transcription of the gene. SAHA causes an accumulation of acetylated histones H3 and H4 in total cellular chromatin by 2 h, which is maintained through 24 h of culture. An increase in the accumulation of acetylated H3 and H4 was detected throughout the p21(WAF1) promoter and the structural gene after culture with SAHA. The level of histone acetylation did not change in chromatin associated with the actin and p27 genes, and their mRNA expression was not altered during culture of T24 cells with SAHA. Thus, the present findings indicate that the induction of p21(WAF1) by SAHA is regulated, at least in part, by the degree of acetylation of the gene-associated histones and that this induced increase in acetylation is gene selective.
 ...
PMID:Histone deacetylase inhibitor selectively induces p21WAF1 expression and gene-associated histone acetylation. 1095 55

Suberoylanilide hydroxamic acid (SAHA) is the prototype of a family of hybrid polar compounds that induce growth arrest in transformed cells and show promise for the treatment of cancer. SAHA induces differentiation and/or apoptosis in certain transformed cells in culture and is a potent inhibitor of histone deacetylases. In this study, we examined the effects of SAHA on the growth of human prostate cancer cells in culture and on the growth of the CWR22 human prostate xenograft in nude mice. SAHA suppressed the growth of the LNCaP, PC-3, and TSU-Pr1 cell lines at micromolar concentrations (2.5-7.5 microM). SAHA induced dose-dependent cell death in the LNCaP cells. In mice with transplanted CWR222 human prostate tumors, SAHA (25, 50, and 100 mg/kg/day) caused significant suppression of tumor growth compared with mice receiving vehicle alone; treatment with 50 mg/kg/day resulted in a 97% reduction in the mean final tumor volume compared with controls. At this dose, there was no detectable toxicity as evaluated by weight gain and necropsy examination. Increased accumulation of acetylated core histones was detected in the CWR22 tumors within 6 h of SAHA administration. SAHA induced prostate-specific antigen mRNA expression in CWR22 prostate cancer cells, resulting in higher levels of serum prostate-specific antigen than predicted from tumor volume alone. The results suggest that hydroxamic acid-based hybrid polar compounds inhibit prostate cancer cell growth and may be useful, relatively nontoxic agents for the treatment of prostate carcinoma.
 ...
PMID:Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses the growth of prostate cancer cells in vitro and in vivo. 1101 44


1 2 3 4 5 6 7 8 9 10 Next >>