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

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

We have investigated the expression of Mr 53,000 protein (p53) in total RNA isolated from human peripheral blood mononuclear cells stimulated by phytohemagglutinin, in serum-stimulated human diploid fibroblasts, and in normal and tumor cells of human epithelial colon tissue. We have found that the expression of p53 messenger RNA is growth regulated in human cells following kinetics similar to that previously shown in mouse 3T3 cells, and is increased in the large majority of colon adenocarcinomas in comparison to adjacent normal mucosa and adenoma. This increased expression of p53 is accompanied by a nearly proportional increase in the expression of histone H3. As the expression of histone H3 is restricted to the S phase of the cell cycle and therefore measures the growth fraction of a given population, we suggest that the increased expression of p53 observed in the large majority of colon tumors simply reflects the increased number of cycling cells frequently found in a neoplastic tissue. At variance with these findings a true overexpression of p53 was detected in one SV40-transformed human fibroblasts cell line.
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PMID:Growth-dependent expression of human Mr 53,000 tumor antigen messenger RNA in normal and neoplastic cells. 301 34

The effect of mitomycin C on the accumulation of specific mRNAs was studied in asynchronously growing Swiss 3T3 cells, as well as in synchronously growing serum stimulated ts13 cells (a temperature-sensitive mutant from the BHK cell line). It was observed that the steady-state level of p53 RNA experienced some increase in 3T3 cells treated for 24 h with the drug. In addition, mitomycin when applied to serum stimulated ts13 cells increased the level of p2F1 RNA. Mitomycin diminished the level of core histone H3 RNA, a finding consistent with the inhibitory action of this compound on DNA replication.
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PMID:Effect of mitomycin C on specific gene transcript levels in cultured mammalian cells. 312 65

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

We have investigated the expression of six growth-regulated genes (c-myc, c-myb, p53, 4F1, 2F1, and ornithine decarboxylase) and the S-phase-specific histone H3 gene in acute myeloid and lymphoid leukemic cells. We have purposely chosen three growth-regulated protooncogenes that share similar biological features and three gene sequences that have in common the cell cycle dependence of their expression in cells of different tissue and in different species. The level of expression was determined by measuring the amounts of specific RNA by Northern blot analysis. Levels of expression of the six growth-regulated genes were compared to the level of expression of the S-phase-specific H3 gene and among themselves. This method distinguishes the increased expression of a growth-regulated gene due to a true altered activation from over-expression which simply reflects an increase in the fraction of cycling cells. We have found that six of 14 patients with acute leukemias have markedly high ratios of c-myc/H3, c-myc/p53, and c-myc/c-myb expression. Two patients with altered c-myc expression have also a high ratio p53/H3. Within the group of cell cycle-dependent genes the ratios of expression seem in the overall much more regular with the clear exception of a patient with acute myelogenous leukemia in which the ratios 4F1/H3 and 2F1/H3 are significantly increased. A possible interpretation of these findings is that the fraction of noncycling leukemic cells that often constitute the majority of the entire leukemic population is in some cases in a true resting state, whereas in other cases heterogeneous degrees of growth arrest might occur. The altered expression of c-myc seems the feature most commonly associated with this putative growth arrest of leukemic cells suggesting that this gene may contribute to the impairment of proliferative control that is associated with the leukemic phenotype.
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PMID:Expression of growth-regulated genes in human acute leukemias. 375 69

We have investigated the expression of growth-regulated genes in tsJT60 cells, a temperature-sensitive (ts) mutant of Fischer rat cells, which, on the basis of its kinetic behavior, can be classified as a G0 mutant. It grows normally at 34 degrees C and also at 39.5 degrees C if shifted to the higher temperature during exponential growth. However, if the cell population is first made quiescent by serum deprivation, subsequent stimulation by serum induces the cells to enter S phase at 34 degrees C but not at 39.5 degrees C. A panel of growth-regulated genes was used that included three protooncogenes (c-fos, c-myc, and p53), several genes that are induced in G0 cells stimulated by growth factors (beta-actin, 2A9, 2F1, vimentin, JE-3, KC-1, and ornithine decarboxylase), and an S-phase gene (histone H3). The expression of these growth-regulated genes was studied in both tsJT60 cells and its parental cell line, rat 3Y1 cells. All the genes tested, except histone H3, are similarly induced when quiescent tsJT60 cells are stimulated by serum at either permissive or restrictive temperatures. These results raise intriguing questions on the nature of quiescence and the relationship between G0 and G1 in cells in culture.
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PMID:Expression of growth-regulated genes in tsJT60 cells, a temperature-sensitive mutant of the cell cycle. 380 8

We have investigated the inducibility of several cell cycle-dependent genes (plus control sequences, not expressed in a cell cycle-dependent manner) in the presence of cycloheximide, an inhibitor of protein synthesis. The genes studied include: 1) five cDNA clones that are preferentially expressed in the G1 phase of the cell cycle: KC-1, JE-3, 2F1, 4F1 and 2A9; 2) one gene preferentially expressed in late G1/S phase: histone H3; and 3) the cell cycle-dependent oncogene p53. All the genes studied are induced by serum even in the presence of cycloheximide. Previous results in the literature have shown that 2 other oncogenes, c-myc and c-fos, can be induced by growth factors in the presence of cycloheximide. Together with our results, these findings indicate that protein synthesis is not required for the induction of at least nine cell cycle genes by growth factors.
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PMID:The effect of cycloheximide on the expression of cell cycle dependent genes. 406 32

As in most other tumor types, expression of mutated or phenotypically altered p53 is a common occurrence in head and neck carcinogenesis. Since the prognosis for many head and neck tumor patients is severely affected by the occurrence of multiple primary and secondary tumors, we have analyzed the phenotype and genotype of p53 in squamous and respiratory epithelia either adjacent to or at significant distance from the primary tumors. Many tumor patients showed multifocal overexpression of the p53 protein in a variety of these epithelia. Overexpression of p53 correlated with increased proliferation and dedifferentiation, as demonstrated by immunohistochemistry and in situ hybridization using histone H3 and cytokeratin-specific probes. Polymerase chain reaction-single-strand conformation polymorphism analysis and sequencing of p53 DNA, amplified from these biopsies after immunostaining and microdissection, confirmed and extended these findings. We have identified different mutations in p53 in different tumor-distant epithelia from the same patients. The data indicate that mutation of p53 is an early event in head and neck carcinogenesis, preceding signs of overt neoplasia, and that different mutations in p53 in multiple foci may provide a molecular basis for the development of multiple tumors.
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PMID:Expression of mutated p53 occurs in tumor-distant epithelia of head and neck cancer patients: a possible molecular basis for the development of multiple tumors. 836 14

Mutation of the tumor suppressor gene p53 is the most frequent genetic alteration of human tumors. Our systematic immunohistochemical analysis of the p53 phenotype and the comparison to proliferation and differentiation has revealed that over 50% of the squamous cell carcinomas of the head and neck show p53 accumulation of aberrant p53 protein. Normal epithelia did not show p53 accumulation and benign lesions only in exceptional cases. Expression of aberrant p53 was invariably confined to dysplastic cells in close vicinity to the tumor and to invasive, dedifferentiated tumor cells with high proliferative potential, as revealed by expression of the histone H3 gene and of the simple epithelial type cytokeratins. We discuss the possible clinical value of the immunohistochemical screening of tumor patients for the status of the p53 gene.
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PMID:[Significance of aberrant p53 protein in head-neck tumors and its effect on proliferation and differentiation]. 833 85

This study investigates whether insulin (a differentiation factor for lens epithelial cells) acts as a survival factor. In the absence of insulin, 6-day embryonic chicken lens epithelial explants undergo apoptosis as shown by changes in cell morphology, DNA fragmentation, and loss of trypan blue exclusion. Insulin inhibits these changes and promotes survival of the cells. Aurintricarboxylic acid suppresses the apoptosis of lens explants. In contrast to 6-day embryonic explants, 19-day embryonic explants survive in the absence of insulin, presumably due to an endogenous survival factor. To explore the mechanism of the action of insulin as a survival factor for 6-day embryonic lens explants, we compared the pattern of cell cycle markers (c-fos, c-jun, c-myc, p53, histone H3, thymidine kinase, and cyclin B) in both apoptotic and differentiating lens explants. In the presence of insulin, the expression of c-fos and c-jun was down-regulated after an initial induction. Expression of these genes was also induced in the absence of insulin, but mRNA levels remained elevated as the cells underwent apoptosis. In contrast, expression of c-myc, p53, histone H3, thymidine kinase, and cyclin B showed only minor differences in differentiating and apoptotic cells. Since c-fos and c-jun have been shown to play a role in apoptosis in other cell types, the ability of insulin to regulate expression of these genes may be central to its ability to act as a survival factor for lens epithelial cells.
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PMID:Insulin regulates expression of c-fos and c-jun and suppresses apoptosis of lens epithelial cells. 854 23


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