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

Correlation between the expression of growth factor/receptor systems or the alterations of tumor suppressor genes and biological malignancy of gastric cancer was described. Overexpression of many growth factors/receptors, such as EGF, TGF alpha, EGF receptor and ERBB2, and reduction of type I receptor for TGF beta may be linked with new prognostic factors of gastric carcinomas. The expression of cripto, a novel gene of EGF family, shows a tendency to correlate with tumor staging of well differentiated gastric adenocarcinomas. p53 gene abnormalities take place in 60% of gastric carcinomas including early stage carcinoma. Loss of heterozygosity on chromosomes 1q, 7p and 7q is frequently observed in advanced gastric carcinomas of well differentiated type. Molecules which regulate tumor invasion and metastasis such as nm23, tissue inhibitor of metalloproteinase (TIMP) and endogenous galactoside-binding lectin may provide for prognostic factors of gastric cancer.
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PMID:[New prognostic factors in human gastric carcinomas]. 134 86

The p53 gene has been associated with malignant transformation as well as "anti-oncogene" activity. In the present report expression of p53 in resting and activated human blood monocytes and lymphocytes is analyzed. It is found that human monocytes freshly isolated by continuous percoll gradient centrifugation contained detectable level of p53 mRNA. Stimulation of monocytes by potent activation inducer Staphylococcus Aureus Cowan I for 3-5 hr caused disappearance of r53 mRNA. In contrast, induction of high level of TNF-alpha mRNA was detected. Addition of cycloheximide had no effect on p53 mRNA content in stimulated monocytes, and caused disappearance of mRNA in resting cells. In lymphocytes cultures p53 mRNA was absent in freshly isolated cells and in resting lymphocytes cultured for 20 hr. Activation of lymphocytes by lectin caused accumulation of p53 mRNA. We suggest that r53 gene regulation and functions might be different in human monocytes and lymphocytes.
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PMID:[Differences in anti-oncogene p53 expression in human monocytes and lymphocytes in vitro]. 144 38

A recently established model for local breast cancer recurrence using the 13762NF rat mammary adenocarcinoma was used to evaluate biologic and biochemical properties related to clinical outcome for this class of tumors. Sublines isolated from local tumor regrowths following surgical resection differed from each other and from the 'parental' cell lines for multiple phenotypes, including metastatic propensity. Local recurrence- and primary tumor-derived sublines were examined by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), lectin binding to electrophoretically separated proteins, and lactoperoxidase-catalyzed cell surface iodination; and differential protein patterns were compared to tumor progression and metastatic potential. 2D-PAGE revealed several quantitatively different spots which correlated with lung colonization potential. In particular, quantities of an apparently unique, non-cell-surface protein, P50.9 (Mr approximately 50,900, pI approximately 7.3) correlated inversely with metastatic propensity, suggesting that it may be associated with, among other possibilities, the negative regulation of the metastatic phenotype. P50.9 was unrelated to four similarly sized metastasis-associated proteins--tumor autocrine motility factor; the rat analog of tumor suppressor, p53; rat cytokeratin 14 or procathepsin D--as determined by amino acid analysis. A major wheat germ agglutinin binding sialoglycoprotein, gp93 (Mr approximately 93,000), was present in smaller amounts as cells were passaged in vivo and re-established as in vitro cultures [MTF7 greater than 'primary' tumor-derived lines (sc1, sc3) much greater than local recurrence-derived lines (LR1, LR1a, LR3, LR4, LR5, LR6)]. Besides cell surface glycoprotein losses, two of six local recurrence-derived sublines expressed a wheat germ agglutinin-binding sialoglycoprotein, gp110 (Mr approximately 110,000), previously undetected on any of the other cell lines including the parental populations. gp110 was found in LR3 and LR6 which were relatively highly metastatic; however, correlation with metastatic potential failed because gp110 was not present on the metastatic parental cell line, MTF7. These results demonstrate specific quantitative and qualitative protein differences associated with the selection of locally recurrent mammary tumors.
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PMID:Tumor progression- and metastasis-associated proteins identified using a model of locally recurrent rat mammary adenocarcinomas. 222 68

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 assembled a system for testing the hypothesis that changes in glycoconjugate production represent markers for defining developmental, spatial, and environmental influences on the proliferation and differentiation programs of various mouse gut epithelial cell lineages. Multilabel immunohistochemical methods were used to survey the interactions of purified lectins with 1) normal fetal, neonatal, and adult FVB/N mouse gut, 2) gastric and intestinal isografts harvested at various developmental stages, and 3) transgenic mouse models of intestinal epithelial cell hyperplasia, dysplasia, and/or neoplasia. As a demonstration of the system's utility, we used the recently purified, alpha-N-acetyl-D-galactosamine-specific, Moluccella laevis lectin (MLL). In the adult FVB/N mouse stomach, MLL only recognizes glycoconjugates produced by a population of nonproliferating neck and prezymogenic cells that occupy a pivotal point in the complex, migration-associated differentiation program of the zymogenic cell lineage. In the developing FVB/N stomach, MLL binds to members of the zymogenic and pit lineages even before morphogenesis of gastric units is completed. Expression of MLL epitopes in pit cells is restricted to the period before the gastric epithelium has completed its morphoregulatory program. Analysis of gastric isografts indicates that these lineage- and developmental stage-specific patterns of glycoconjugate accumulation are not influenced by normal luminal contents. In the adult FVB/N intestine, MLL binding can be used to operationally define variations in the differentiation programs of 1) members of the enteroendocrine and goblet cell lineages during their migration along the crypt-to-villus axis and 2) cells comprising the follicle-associated epithelium overlying Peyer's patches. Accumulation of MLL epitopes in villus-associated enterocytes does not appear to be affected when these cells are induced to reenter the cell cycle by simian virus 40 large T antigen (SV40 TAg). MLL reactivity is not diminished when enterocytes begin to dedifferentiate as a result of production of SV40 TAg, human K-rasVal12, and a dominant negative human p53 mutant. The lack of change in MLL binding properties may reflect the brief residence time of enterocytes on the villus. These results indicate that glycoconjugate production represents a very useful tool for studying gut epithelial cell biology. Preliminary studies suggest that this is also true in the human gut.
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PMID:Moluccella laevis lectin, a marker for cellular differentiation programs in mouse gut epithelium. 753 54

Regulation of p53 gene expression at the post-transcriptional level was investigated during growth induction of human peripheral blood mononuclear cells (PBMCs). Freshly isolated PBMCs, which are in the Go phase of the cell cycle, were shown to express low levels of p53 mRNA that was rapidly degraded with a half life of 1 h. The rapid decay of p53 mRNA in quiescent PBMCs was dependent on global protein synthesis as treatment with cycloheximide resulted in stabilization of the p53 message. PBMCs were stimulated to enter the cell cycle by treatment with a combination of the mitogenic lectin phytohemagglutinin (PHA) and phorbol ester (TPA). Progressive stabilization of the p53 message occurred in PBMCs during growth induction. By 24 h of incubation in the presence of PHA and TPA, the half life of p53 mRNA was 6 h and p53 mRNA steady state levels were increased 4.5 to 5.0-fold. p53 protein was not detected in quiescent PBMCs, but was readily detected in PBMCs stimulated for 24 h with PHA and TPA. Stabilization of p53 mRNA was observed in PBMCs treated with either PHA or TPA, but to a lesser degree than when PHA and TPA were used as co-stimulants. These results indicate that differential degradation of p53 messenger RNA occurs in quiescent vs mitogen stimulated PBMCs and suggest that post-transcriptional regulation importantly contributes to increased p53 mRNA steady state levels as PBMCs enter the cell cycle.
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PMID:Post-transcriptional regulation of the p53 tumor suppressor gene during growth-induction of human peripheral blood mononuclear cells. 784 76

A rare case with a metastasizing teratocarcinoma of the lung is presented. The 51-year-old man developed a central tumour mass in the left lung. Bronchoscopy and intraoperative sections of an involved lymph node supplied histomorphologic findings that are indicative for an epidermoid carcinoma. Further detailed analysis resulted in the final classification as a malignant teratoma. This rare tumour was further analyzed for the expression of various cellular characteristics, namely binding sites for various carbohydrates including sequences such as saccharides of the ganglioside GM1, for erythropoietin, tumour necrosis factor-alpha, and epidermal growth factor. Immunohistochemistry was used to determine the expression of neuron-specific enolase, carcino-embryonic antigen, calcyclin, epidermal growth factor, beta-HCG, AFP, p53 protein, and heparin-specific lectin. The results revealed similarities to a case with a pulmonary blastoma, and remarkable differences to that of epidermoid carcinoma cases. Similar results were seen in the DNA- and syntactic-structure analysis. The tumour reported on here should, therefore, be considered as a rare, specific entity of primary lung malignancies.
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PMID:Malignant teratoma of the lung with lymph node metastasis of the ectodermal compartment: a case report. 831 68

Human p53 was expressed in E. coli, purified, labeled with fluorescein iodoacetamide (IAF) and characterized for sequence-specific DNA binding and epitope disposition. Injected into the cytoplasm or nuclei of 3T3 cells IAF-p53 was imported into or exported from nuclei within minutes. Import was inhibited by coinjection of the lectin wheat germ agglutinine (WGA). In contrast, the peptide-protein conjugate NLS-HSA carrying the nuclear localization sequence (NLS) of the SV40 T antigen was only imported but not exported. 3T3 polykaryons were injected with IAF-p53 and photo-bleached by Scanning Microphotolysis in such a manner that only a single nucleus per polykaryon remained non-bleached. IAF-p53 was found to migrate rapidly (halftime 10 min) from non-bleached into bleached nuclei, while NLS-HSA did not. In digitonin permeabilized cells IAF-p53 was imported into nuclei. When removed from the medium after nuclear accumulation IAF-p53 was exported from the nuclei. Nuclear import and export of IAF-p53 both were rapid (halftimes of a few minutes, 22 C) and strongly inhibited by WGA or incubation on ice. NLS-HSA was only imported but not exported. We conclude that the nucleocytoplasmic transport of p53, in contrast to that of NLS-HSA, is bidirectional and that transport in both directions is carrier mediated and energy dependent. These results suggest that p53 contains nuclear export signals (NES) in addition to import signals (NLS) and thus open new views on the potential regulation of p53 cellular fractions.
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PMID:The tumor suppressor p53 is subject to both nuclear import and export, and both are fast, energy-dependent and lectin-inhibited. 913 84

Immunohistochemically assessed p53 expression was correlated with overall survival in 20 patients with glioblastoma multiforme. Various epitopes of p53 molecule were detected using DO-1, DO-7, CM-1 and BP-12-53 antibodies, proliferative activity was estimated using anti-PCNA and anti-Ki-67 antibodies and assessment of glycosylation changes using lectin histochemistry completed the study. The results show a statistically significant correlation between DO-1 binding and survival. However, we failed to find any similar statistically significant relationship using other antibodies used in this study. Nor the intensity of proliferative activity show any correlation with either p53 expression or overall survival. Glycosylation in glioblastoma multiforme cells reflected unspecific changes in tumor cells regardless of any relationship to p53 expression. The findings do not provide clear evidence for the predictive value of p53 expression. On the other hand, relatively larger numbers of p53 immunonegative cases may indicate that other mechanisms are involved in the development of this tumor.
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PMID:Expression of p53 in glioblastoma multiforme cells: relationship to survival, proliferation and glycosylation. 944 87

Galectin-3 is a galactose-binding lectin that has been found in several mammalian tissues. Galectin-3 gene is expressed in a wide range of normal and tumoral cells. In the case of myeloid cells, its expression correlates with the differentiation of monocytes to macrophages. In the case of cancer cell lines, its expression correlates with tumorigenicity and metastatic potential. The regulation of the expression of this gene is still largely unknown. The rabbit galectin-3 gene has been isolated and characterized. Its structure revealed an organization similar to that of the murine galectin-3 gene. The genomic sequences located upstream from its 5' end, upon insertion upstream from a promoter-free reporter gene, exhibited a strong promoter activity. This activity was upregulated upon treatment of transfected smooth muscle cells with phorbol 12-myristate 13-acetate (PMA) as well as upon transfection with a EJ/ras encoding plasmid. Conversely, it was downmodulated upon transfection with wild-type p53 but not with mutated p53. The regulatory sequences involved in the positive regulation of the gene were located upon serial deletion experiments.
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PMID:Modulation of the expression of the rabbit galectin-3 gene by p53 and c-Ha-ras proteins and PMA. 945 10


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