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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of three growth-regulated protooncogenes, c-myc, c-myb, and p53, and the S-phase-specific histone H3 gene, was compared in bone marrow cells from multiple myeloma patients and normal controls by measuring the amount of specific RNA by Northern blot analysis. Four samples contained at least 72% of myeloma cells, one sample 43%, and one 11%. Expression of the protooncogenes was similar in normal and myeloma bone marrow cells, whereas that of histone H3 gene was significantly reduced (between 10 and 15 times) in samples containing at least 43% of malignant plasma cells and not detectable in those containing more than 72% of neoplastic cells. Protooncogene levels of expression were compared to those of the H3 gene to distinguish the increased expression of a growth-regulated gene due to a true deregulation from overexpression reflecting solely an increase in the fraction of cycling cells. The ratios of expression of protooncogenes to histone H3 were markedly increased in multiple myeloma cells; the highest ratios were found in the patients with the highest number of malignant plasma cells. These results suggest that the expression of three growth-regulated oncogenes (c-myc, c-myb, p53) is altered in myelomatous plasma cells.
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PMID:Altered expression of growth-regulated protooncogenes in human malignant plasma cells. 266 53

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.
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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.
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PMID:Sequential expression of protooncogenes during lectin-stimulated mitogenesis of normal human lymphocytes. 301 40

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.
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PMID:Hexamethylene bisacetamide-induced differentiation of transformed cells: molecular and cellular effects and therapeutic application. 304 66

We have examined 44 cases of human colonic and rectal carcinomas for structural rearrangement and amplification of c-myc, N-myc, L-myc, c-myb and p53 oncogenes. DNA hybridization showed evidence of c-myc amplification in only one of the samples tested. In addition, the same tumour also showed a rearrangement immediately 3' to the c-myc locus. No rearrangement could be found at the c-myc locus in the other 43 cases. Moreover, our molecular analysis of N-myc, L-myc, c-myb and p53 genes indicated no relevant alteration of the copy number and/or genomic structure of these nuclear oncogenes. Thus, at least in human colorectal malignancies, it is unlikely that nuclear oncogene structural alterations and/or amplification plays a major role in tumour induction or progression.
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PMID:Nuclear oncogene amplification or rearrangement is not involved in human colorectal malignancies. 318 Dec 52

The authors have assayed the level of expression of several cell-cycle related genes in several populations of circulating myeloid leukemic blast cells. The genes explored included oncogenes such as c-myc, c-myb, p53, and cell-cycle-related genes such as vimentin, calcyclin, ornithine decarboxylase (ODC) and histone H3. Particular attention was given to analysis of the relationship existing between the mRNA levels of the histone H3 gene, which is expressed specifically in the S phase of the cell cycle, and the levels of other genes that are expressed in different stages of the G1 phase. Remarkable differences were observed among the different cases indicating that a differential expression of cell-cycle-related genes characterizes many acute leukemias. This differential expression is reflected in an altered ratio among G1-related genes and the H3 histone gene. The large fraction of leukemic cells which does not express histone H3 and therefore is functionally noncycling, shows a heterogeneous pattern of G1-related gene expression. This reflects the inability of most leukemic cells to progress through the G1 phase into the S phase of the cell cycle. This inability represents an abnormality of the cell cycle. It is concluded that the study of the expression of cell-cycle genes and protooncogenes in in understanding how leukemic cells enter a state of proliferation arrest, which appears to occur in a large fraction of leukemic cells.
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PMID:Expression of oncogenes and cell cycle related genes in acute and chronic leukemias. 319 78

Six colon cancer cell lines, 13 colon tumors and ten normal colon tissues were analyzed for RNA expression using probes for c-myc, c-k-ras, c-myb, and c-fos and for the p53, TGF-alpha, and EGF receptor genes. No aberrant transcripts were detected. Levels of expression in tumors ranged from two-fold below that of normal tissue when the v-fos probe was used to 10 fold above the normal level when the c-myc probe was used. Enhanced c-myc expression was also observed in the cell lines. Southern and DNA dot blot analyses revealed c-myc amplification in three of the six cell lines.
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PMID:Oncogene expression in adenocarcinomas of the colon and in colon tumor-derived cell lines. 328 75

MELC may be induced to terminal erythroid differentiation by HMBA and other agents. Although the mechanism is not known, changes in cell function and gene expression can be identified during an early "latent" period, prior to commitment to terminal differentiation. These include a decrease in diacylglycerol concentration and in Ca+2 and phospholipid-dependent protein kinase C activity, accompanied by suppression of c-myb and c-myc gene transcription, a fall in p53 protein, and an increase in c-fos mRNA. Commitment is first detected by 12 hours and is associated with persistent suppression of c-myb gene transcription. Transcription of the erythroid-specific genes, alpha 1 and beta maj globin, is increased 10- to 30-fold, whereas synthesis of rRNA is suppressed, and there is activation or suppression of a number of additional genes that remain to be characterized. The potential regulatory roles of changes in protein kinase C activity and in proto-oncogene expression in initiating and sustaining the process of differentiation also remain to be elucidated.
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PMID:Induced erythroleukemia differentiation: cellular and molecular aspects. 331 Dec 22

HMBA induces MEL cells to terminal erythroid differentiation. HMBA causes a decrease in diacylglycerol concentration, a decrease in Ca+2 and phospholipid-dependent protein kinase C activity (within 2 hr). There is an early (within 1-2 hrs) suppression of c-myb and c-myc gene transcription and an increase in c-fos mRNA (within 4 hrs). During the early or "latent" period there is no detectable commitment of MELC to terminal cell division or expression of differentiated genes such as alpha 1 or beta maj globin genes. HMBA-induced commitment to terminal differentiation is detected by 12 hrs and over 95% become committed cells by 48-60 hrs. Commitment is associated with persistent suppression of c-myb gene transcription and elevated levels of c-fos mRNA, whereas the level of c-myc mRNA returns to that of uninduced cells. By 36-48 hrs, transcription of the alpha 1 and beta maj globin genes increases 10-30 fold, and that of rRNA genes is suppressed. Changes in expression of c-myb, c-myc, c-fos and p53 genes that occur early during HMBA-induced differentiation may be important in the multistep process involved in commitment of MEL cells to terminal differentiation. Continued suppression of c-myb gene expression may be required for terminal differentiation of these cells.
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PMID:Induction of transformed cells to terminal differentiation. 332 66

HMBA induces MELC to terminal erythroid differentiation. The mechanism of HMBA action is not known. Culture with HMBA causes changes in gene expression which occur during the early "latent period", that is, prior to commitment to terminal differentiation. The inducer causes a decrease in diacylglycerol concentration, a decrease in Ca+2 and a decrease in phospholipid-dependent protein kinase C activity (within 2 hr) (Figure 2). There is an early suppression (within 1-2 hrs) of c-myb and c-myc gene transcription and an increase in c-fos mRNA (within 4 hrs). HMBA-induced commitment to terminal differentiation is detected by 12 hrs and over 95% become committed cells by 48 to 60 hrs. Commitment is associated with persistent suppression of c-myb gene transcription and elevated levels of c-fos mRNA whereas the level of c-myc mRNA returns to that of uninduced cells. By 36 to 48 hrs, transcription of alpha 1 and beta maj globin genes is increased 10 to 30 fold, while that of rRNA genes is suppressed. It is not yet clear how the protein products of proto-oncogenes elicit or modify cellular responses. Changes in expression of c-myb, c-myc, c-fos and p53 genes which occur during HMBA-induced differentiation, as well as in several other systems, suggest that products of these genes may have a role in regulating expression of multiple genes. One possible application of the established pattern of HMBA-induced modulation of gene expression during MELC differentiation may be in following the effects of cyto-differentiation agents during treatment of cancers. Phase I and Phase II chemical trials have been initiated to evaluate HMBA as a cytodifferentiation agent in human neoplasms (65). For most human tumors, assay for cytologic evidence of induced differentiation is difficult at best. Following the effects of a differentiation inducing agent by determining c-myc, or c-myb, mRNA levels may provide useful indicators of biological activity of HMBA and be a basis for evaluating whether continued administration of the agent is of interest in terms of potential clinical efficacy.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Changes in gene expression during hexamethylene bisacetamide induced erythroleukemia differentiation. 348 Oct 77


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