Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of oncogenes (c-myc, c-fos, c-Ki-ras, c-Ha-ras, and p53) was examined by Northern blot analysis using freshly isolated human colorectal and gastric cancers and noncancerous portions as the controls. Remarkably high levels of c-myc expression were found in colorectal cancers (eight of 11), but not in gastric cancers. High levels of c-myc expression were also detected in colorectal polyps and in metastatic liver tumors. In colorectal polyps, the transcript levels significantly correlated with the histologic malignancy and the size. In contrast, neither c-fos nor c-Ki-ras was overexpressed in colorectal and gastric cancers, and transcripts of c-Ha-ras and p53 were not evident in any tissue examined. In light of these observations the c-myc expression may be specifically associated with the evolution of colorectal cancer as well as progression and maintenance stages, hence may prove to be a useful marker to evaluate the malignant potential of colorectal polyps.
 ...
PMID:Expression of c-myc oncogene in colorectal polyps as a biological marker for monitoring malignant potential. 274 65

Stimulation of beta-adrenoreceptors in rat parotid acinar cells in vitro by the beta-adrenergic agonist isoproterenol induces steady-state levels of c-fos mRNA and c-fos protein in these cells. A dramatic increase in the steady-state levels of c-fos mRNA was observed at 60 min, followed by a decrease at 2 h with a second peak at 4 h. c-fos induction in rat parotid acinar cells in vitro seems to be mediated by cAMP. Increased levels of p53 and c-myc mRNA were detected only at 60 min. c-abl and c-sis were also induced by isoproterenol but in a pattern different from that seen with c-fos. c-abl was the only oncogene in rat parotid gland which showed increased expression after chronic isoproterenol treatment of rats. In rat parotid acinar cells we observed no correlation between DNA synthesis and c-fos induction.
 ...
PMID:Regulation of proto-oncogenes in rat parotid acinar cells in vitro after stimulation of beta-adrenergic receptors. 284 68

Stimulation of beta-adrenoreceptors in the RSMT-A5 epithelial cell line is accompanied by an early and transient increase in the expression of the proto-oncogene c-fos. Maximal induction was at 30 min, returning to basal levels after 2 h. Similar results were obtained when cells were incubated with 8-bromo-cAMP. The induction of c-fos is specific since the expression of p53, a transformation-related gene, is not modulated by isoproterenol or 8-bromo-cAMP. The increase in c-fos gene expression is not associated with proliferative activity in these epithelial cells.
 ...
PMID:Beta-adrenergic regulation of c-fos gene expression in an epithelial cell line. 284 42

A comparative study on the expression of nuclear and cytoplasmic oncogenes was carried out using the Northern blotting technique, in Rauscher virus induced primary leukemias and the more malignant transformed cell lines derived from them. The latter grow permanently in vitro. Hyperplastic spleens obtained from mice recovering from anemia were analysed as controls. In addition to the detection of mRNAs, Southern blotting was carried out to observe whether rearrangement or amplification of oncogenes had occurred. The results show that the nuclear oncogenes c-myc, c-myb and p53 are strongly expressed in leukemic tissue, whereas c-fos transcripts show a much weaker hybridization. The expression of two of these oncogenes, c-myc and c-myb was followed during differentiation in myeloid leukemic cells and showed a gradual decrease when compared with the actin gene, which is constitutively transcribed. A large number of cytoplasmic oncogenes is expressed in the leukemic cells lines, i.e. c-abl, c-fms, c-fes, c-src, c-ros, c-H-ras, c-K-ras and N-ras. Of these, transcripts coding for c-abl and c-src were absent in blast cells of acute erythroid leukemias. Transcripts coding for c-erb, c-mos and c-sis could also not be detected. A number of putative oncogenes which are reported to play a role in Moloney and Friend virus induced leukemias for instance pim-1, fis-1, fim-1 and fim-2 were also used for screening. Only expression of pim-1 in Rauscher virus induced myeloid leukemic cells and in primary acute erythroid leukemias could be observed. At the DNA level no rearrangement or amplification of any of the oncogenes investigated could be detected. The results show that a number of oncogenes are expressed simultaneously in the same leukemic tissue or cell lines. It therefore seems likely that the presence of transcripts of different oncogenes is associated with the progression of leukemia, but is not the primary cause of leukemogenesis or of the transformation of these cells into established cell lines.
 ...
PMID:Oncogene expression in Rauscher murine leukemia virus induced erythroid, myeloid and lymphoid cell lines. 291 75

The proliferation of non-neoplastic T lymphocytes is regulated, in part, by the coordinated expression of genes encoding T-cell growth factor (interleukin 2, IL2), IL2 receptors (IL2R), and transferrin receptors (TFR). In addition to growth factors and their receptors, protooncogenes may regulate lymphocyte proliferation. We used cloned cDNAs homologous to 21 different protooncogenes to screen for their expression at the mRNA level in human peripheral blood mononuclear cells (PBMC) stimulated with the mitogenic lectin phytohemagglutinin (PHA), and we compared the time course of accumulation of mRNAs for these protooncogenes to that of mRNAs for the IL2, IL2R, TFR, and histone H3 genes. mRNAs for c-abl, c-ets, c-yes, and N-ras were present in unstimulated PBMC. After stimulation of PBMC by PHA, we detected marked increases within 10 min in the levels of mRNA for c-fos and c-myc; within 6 hr for IL2 and IL2R mRNAs; within 14 hr for c-myb, p53, N-ras, and TFR mRNAs; and within 24-36 hr for H3 mRNA. Expression of c-abl, c-ets, and c-yes increased gradually following stimulation with PHA. None of the other protooncogenes tested was expressed in PBMC. Addition of the protein synthesis inhibitor cycloheximide, before the addition of PHA to cultures, abolished the PHA-induced accumulation of mRNAs for c-myb, N-ras, and TFR, but not of mRNAs for c-fos, c-myc, IL2, and IL2R. These data indicate that c-fos, c-myc, IL2, and IL2R belong to a group of genes expressed early, whereas c-myb, N-ras, and TFR belong to a group of genes expressed later in PHA-activated PBMC, and that the products of the c-fos and c-myc protooncogenes are not required for expression of IL2 or IL2R genes. Addition of purified IL2 augmented the expression of the later-expressed genes c-myb, p53, N-ras, and TFR in PHA-stimulated cultures of PBMC, as well as of the early genes c-myc and IL2R, but not of c-fos and IL2, thus suggesting that PHA and IL2 stimulate the expression of overlapping, but nonidentical, sets of genes in PBMC.
 ...
PMID:Sequential expression of protooncogenes during lectin-stimulated mitogenesis of normal human lymphocytes. 301 40

The effects of cyclosporine were examined on gene expression induced in T lymphocytes by mitogenic lectins and interleukin 2 (IL-2). Used at concentrations that inhibited proliferation of human peripheral blood lymphocytes by approximately 90%, CsA suppressed, to different extents, the phytohemagglutinin-stimulated expression of various genes, with levels of mRNAs for IL-2 being inhibited by approximately 100%, c-myc and N-ras by approximately 80%, and c-fos and IL-2 receptors by approximately 50%. Comparisons of the actions of CsA on gene expression in a cloned murine T cell (L2), stimulated with concanavalin A or IL-2, demonstrated that CsA specifically blocked the accumulation of mRNAs for the c-myc and p53 protooncogenes when induced by Con A, but not when induced by IL-2. Taken together, these findings indicate that several pathways can control the expression of a particular gene, and suggest that CsA interferes with only some of these regulatory pathways of gene expression in T lymphocytes.
 ...
PMID:Regulation of gene expression in lectin-stimulated or lymphokine-stimulated T lymphocytes. Effects of cyclosporine. 304 99

Hexamethylene bisacetamide (HMBA), a highly polar compound, induces murine erythroleukemia (MEL) cells to express the erythroid phenotype, including cessation of proliferation. Inducer-mediated differentiation of MEL (DS19) cells is a multistep process characterized by a latent period during which a number of changes occur including alterations in ion flux, an increase in membrane-bound protein kinase C (PKC) activity, the appearance of Ca2+ and phospholipid-independent PKC activity in the cytosol, and modulation in expression of a number of genes such as c-myc, c-myb, c-fos and the p53 genes. HMBA-mediated commitment to terminal differentiation is first detected at about 12 hours and increases in a stochastic fashion until over 95% of the population is recruited to terminal differentiation by 48 to 60 hours. Commitment is associated with persistent suppression of c-myb gene expression. By 36 to 48 hours, transcription of the globin genes has increased 10 to 30 fold, whereas transcription from rRNA genes is suppressed. The steroid, dexamethasone, or the tumor promoter, phorbol-12-myristate-13-acetate (TPA), suppress HMBA-induced MEL cell terminal differentiation. These agents appear to act at a late step during the latent period. MEL cell lines derived from DS19 by selection for resistance to vincristine are: 1) induced to commit without a detectable latent period, 2) markedly more sensitive to HMBA, and 3) resistant to dexamethasone or TPA inhibition of HMBA-induced commitment. The data suggests that vincristine-resistant MEL cells express a factor which circumvents essential HMBA-mediated early events. In vitro studies with HMBA provide a basis for the application of HMBA to clinical therapy of human cancers. Clinical trials with HMBA have been initiated.
 ...
PMID:Hexamethylene bisacetamide-induced differentiation of transformed cells: molecular and cellular effects and therapeutic application. 304 66

Two mutant cell lines, R-1 and R-2, have been isolated from EJ/NIH (NIH/3T3 transformed by a human activated c-Ha-ras gene) by treatment with ethyl-methane-sulfonate (EMS). They reveal various characteristics of normal cells, and seem to have reversed to the original cells. Especially, R-1 shows a very flat morphology, complete contact inhibition, anchorage dependent cell growth and no tumorigenecity. Although transformed phenotypes are intensively suppressed, R-1 does not seem to secrete suppressive factors to the parent cell line. The activated c-Ha-ras (EJ-ras) could be detected as a 6.6 kb BamHI fragment in R-1 as well as in EJ/NIH. The level of transcription and translation in R-1 was also the same as that in EJ/NIH. Moreover, the DNA isolated from R-1 cells had a high transforming activity to NIH/3H3, suggesting that R-1 contained the EJ-ras as an activated oncogene. The levels of transcription of c-myc, c-fos, p53 and other ras family genes was unchanged between EJ/NIH and R-1. Further, R-1 cells are resistant to retransformation by EJ-ras, v-src, v-mos and SV40T genes, and DNAs isolated from EJ/NIH or NIH/3T3 could not transform R-1 cells. All these findings suggest that some genes necessary for transformation by EJ-ras, except for c-myc, c-fos, p53 and ras proto-oncogenes, are defective or some inhibitory genes against transformation are enhanced in R-1 cells.
 ...
PMID:[A study on reversion of the human activated c-Ha-ras-transformed cells]. 307 18

The length of the prereplicative period after stimulation of quiescent WI-38 cells is prolonged in proportion to the length of time the cells are incubated prior to serum addition. Previous results from this laboratory have shown that this prolongation does not result from a delay in the induction of events which occur during the G0/G1 transition (i.e. c-fos or c-myc expression) (Owen, T., Cosenza, S., Soprano, D. R., and Soprano, K. J. (1987) J. Biol. Chem. 262 15111-15117). It was the goal of the present studies to examine the expression of other growth-associated genes known to be induced and maximally accumulate later in G1 to identify genes whose expression is coupled to entry into S rather than mitogenic stimulation. In order to do this, the temporal pattern of expression of a variety of growth-associated genes (thymidine kinase, p53, 2A9/calcyclin, ornithine decarboxylase, 4F1/vimentin, and c-Ha-ras) was studied in WI-38 cells stimulated either 12 days or 26 days after plating. We report that the time of induction and maximum accumulation of each of these transcripts, with the exception of c-Ha-ras, was delayed in the 26-day cell group for 10 h, a period of time approximately equal to the length of delay in entry of these cells into S. Thus the expression of these particular genes would appear to be closely coupled in time and sequence to the entry of cells into S. These results suggest that the prolongation of the prereplicative period in WI-38 cells is located in early G1, following the events leading to c-fos and c-myc induction but prior to the induction and maximum accumulation later in G1 of other growth-associated genes such as ornithine decarboxylase and 4F1/vimentin. In addition, these results provide molecular evidence for a definitive programmed order of gene expression during the progression of cells out of G0 through G1 to S.
 ...
PMID:Evidence that the time of entry into S is determined by events occurring in early G1. 313 30

Sodium butyrate has been shown to exert dramatic effects on the growth of cells in culture. It inhibits DNA synthesis, arrests actively proliferating cells in G1 and induces differentiation. The mechanism responsible for these various anti-proliferative effects is presently unknown. We wished to study the effects of sodium butyrate on cell growth at the molecular level, by analyzing the pattern of expression exhibited by several growth-associated genes (e.g., c-fos, c-myc, p53 and thymidine kinase) in Swiss 3T3 cells following treatment with sodium butyrate. Our results suggest that sodium butyrate-induced growth arrest of Swiss 3T3 cells (1) can be distinguished at a molecular level from the arrest brought about by other means of growth arrest; (2) does not result from a generalized mechanism which non-specifically shuts down the expression of growth-associated genes but rather occurs via a more specific mechanism which leads to the reduction in the expression of certain genes (e.g., c-myc, p53, thymidine kinase) while inducing the expression of others (e.g., c-fos, aP2); and (3) may involve one or more of the molecular events leading to adipocyte differentiation.
 ...
PMID:Molecular analysis of sodium butyrate-induced growth arrest. 314 95


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