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)

Flow cytometry (FCM) is a useful method for clinical research of oncogene products since it can analyze proteins quantitatively which are located at cell surfaces or inside of cells. Oncogene products are now under study by FCM not only as tumor markers but also as functioning proteins in carcinogenesis. The examples of oncogene products analyzed by FCM are ras, myc, p53, myb and fos; those of cell-proliferation-related proteins are Ki-67, PCNA and DNA polymerase alpha. In some diseases the relationship between these proteins and disease classification, stage, pathophysiology, or prognosis have been clarified. Using dual color FCM of H-ras p21 and DNA, we analyzed the expression of H-ras p21 in human multiple myeloma and leukemias and found that H-ras p21 levels in multiple myeloma strongly correlated to the prognosis of patients (p = 0.03). When AML cells were stimulated by adding G-CSF, it was found that many cells proliferated but some were dying. The percentage of dying cells was small in one AML case whose myeloblasts showed increased expression of H-ras p21 by G-CSF stimulation. Together with other papers reviewed, it is conceivable that H-ras p21 expression is related to cell proliferation and inhibition of cell autolysis. Thus FCM is useful in the classification of the role of oncogene products in carcinogenesis in clinical cases.
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PMID:[Application of flow cytometry to the study of hematologic disorders: analysis of oncogene products]. 214 49

Activity of p53, H-ras, c-myc and c-fos in psoriatic lesions was studied using monoclonal antibodies (MoAbs) performing a sensitive immunohistochemical method on frozen sections. Normal skin from surgery was used as control. Reactivity of p53, H-ras and c-myc is remarkable in psoriatic plaques but, in contrast, c-fos expression does not show differences compared to control skin. These findings led us to speculate about the importance of cellular oncogenes in the pathogenesis of psoriasis.
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PMID:P53 and oncogenes expression in psoriasis. 253 48

Flow cytometry (FCM) of oncogene products which opens new avenues of cell biological investigation of human neoplasia is being reviewed. Using H-ras p21/DNA dual FCM, patients with DNA-aneuploid multiple myeloma (MM) were examined. The patients whose MM cells expressed high level of H-ras p21 had poor prognosis. Specificity of this assay was appraised extensively. It is not likely that H-ras p21 expressed in MM is of oncogenic form since point mutation of H-ras gene was not reported in B cell chronic lymphocytic leukemia which is closely located to MM in B lymphocyte differentiation lineage. High expression of H-ras p21 in MM seems to be related to cell proliferation and/or differentiation. H-ras p21/DNA dual FCM is applicable to analyse the pathophysiology of tumor cells. FCM analyses of other oncogene products and proteins related to cell proliferation, c-myc, p53 and Ki-67, were also described. Multiparameter FCM analysis is quite suited to examine expression of these proteins in situ.
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PMID:[Flow cytometric analysis of oncogene products]. 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

Protooncogenes play important roles in the regulation of growth and differentiation of normal cells. In this study we have examined the cell cycle-dependent regulation of transcription of various protooncogenes after stimulation of human peripheral blood B lymphocytes. The transcriptional rate of various genes was determined by means of a nuclear run-on assay. We found that several protooncogenes were transcriptionally activated after stimulation (myc, p53, K-ras, H-ras, sis and ets), but with different kinetics of induction. In contrast, some oncogenes, especially those encoding membrane-associated or cytoplasmatic proteins like abl, rel or mil/raf, were transcribed at a relatively constant rate during the cell cycle.
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PMID:Transcription of protooncogenes during stimulation of normal human B lymphocytes. 306 Mar 64

To establish well-characterized cellular reagents for the study of colon carcinoma, we have examined 19 human colorectal carcinoma cell lines with regard to morphology, ultrastructure, expression of tumor-associated antigens, proliferative capacity in vitro, anchorage-independent growth, oncogene expression, tumorigenicity and malignant potential. Cell lines examined were cultured under identical conditions, and in vitro and in vivo analyses were performed in parallel on replicate cultures. Three classes of colorectal cell lines were defined according to their tumorigenicity in nude mice. Class-1 lines formed rapidly progressing tumors in nearly all mice at an inoculum of 10(6) cells. Cell lines belonging to class-2 were less tumorigenic, producing tumors later and at a slower growth rate. Class-3 lines were non-tumorigenic under all experimental conditions tested. By Northern analysis, the oncogenes c-myc, H-ras, K-ras, N-ras, myb, fos and p53 were expressed in nearly all cell lines examined. In contrast, transcripts for abl, src and ros were not detected. The best in vitro predictor of tumorigenicity was colony formation in soft agar. There was no detectable correlation between tumorigenicity and metastatic potential, doubling time in vitro, production of tumor-associated markers, xenograft histology or expression of specific oncogenes.
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PMID:Biological characterization and oncogene expression in human colorectal carcinoma cell lines. 333 74

Eleven different missense and one nonsense mutant-type p53 cDNAs, which have been frequently detected in human colorectal carcinomas, were constructed and examined for their ability to cooperate with activated human H-ras genes, pSK2 and pHs49, in transfection of rat embryo fibroblasts (REF). Each missense mutant-type p53 cDNA with either of the two activated H-ras genes transformed REF with a different frequency of transformation depending on the different kind of mutation, whereas wild-type p53 (with ras), nonsense mutant-type p53 (with ras), as well as mutant-type p53 (alone) and ras (alone), did not transform REF. Six transformed REF cell lines were established from cotransfection with missense mutant-type p53 cDNA and ras gene; all of them exhibiting exogenous human p53 DNA, RNA, protein, and H-ras DNA and RNA. All six transformed cell lines showed both tumorigenicity and lung metastatic potential in nude mice. They also exhibited 92 kilodalton gelatinase activity, which was not detected in parental REF. These results suggest that missense mutations in p53 gene have a role in malignant transformation as well as metastatic potential.
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PMID:Malignant transformation of rat embryo fibroblasts by cotransfection with eleven human mutant p53 cDNAs and activated H-ras gene. 747 55

Wild type p53 can induce cell cycle arrest at specific points in the cell cycle, in particular G1/S, an ability lost by most p53 mutants. We have previously reported that p53 mutant genes can rescue REF52 cells from ras-induced growth arrest and that over expression of wild type p53 inhibits cell growth in these cells. In this paper we examined whether p53 can also induce cell cycle arrest at the G2/M boundary of the cell cycle. To accomplish this we used the REF52 cell line and the temperature sensitive p53val135 mutant allele. Cells were enriched in the late G1 and early S phases before the temperature shift. REF52 cells expressing mutant-p53val135 alone with an activated H-ras gene arrest primarily at the G1/S and G2/M parts of the cell cycle at the restrictive temperature, as determined by flow cytometry analysis. These results suggest that the anti-proliferative activity of p53 may be involved in regulation of the cell cycle at the G2/M restriction point as well as transit through G1/S and initiation of DNA synthesis.
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PMID:Evidence for a second cell cycle block at G2/M by p53. 752 16

Activation of cellular oncogenes and inactivation of anti-oncogenes have been postulated as important mechanisms during hepatocarcinogenesis. This study was conducted to detect abnormal levels of several proto-oncogenes (c-jun, c-fos, c-H-ras) and of the p53 and the alpha-fetoprotein gene in the liver during cirrhosis, a pathological process which predisposes to the development of hepatocarcinoma. Liver tissue from 11 patients with cirrhosis of different etiologies, and seven histologically normal liver fragments taken at the periphery of benign liver tumors of metastases were studied. Transcripts of the various oncogenes and of the alpha-fetoprotein gene were detected by in situ hybridization, and the p53 protein was revealed by immunocytochemistry. No overexpression of any of the mRNA tested or of the p53 protein was found in histologically normal liver in contact with benign or metastatic tumors. In contrast, 10 of the 11 specimens with cirrhosis (90.9%) displayed abnormally high levels of c-H-ras transcripts. Five samples with cirrhosis revealed a moderate increase in the level of c-fos mRNA. Only one case and two cases, respectively, exhibited increased levels of c-jun and alpha-fetoprotein mRNA. No cases were positive for the p53 antigen. Liver-cell proliferation, as assessed by immunocytochemistry with the Ki 67 monoclonal antibody, was low in both the group with cirrhosis and the control groups (0.49% and 0.55% positive cells, respectively). These data demonstrate that activation of c-H-ras mRNA is an almost constant finding in hepatocytes of livers with cirrhosis. This gene overexpression is not linked to hepatocellular proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activation of ras oncogene in livers with cirrhosis. 753 24

To study the immune response against oncogene-transformed tumors, C3H/HcN mouse embryo fibroblasts (MEF) were transfected with an activated allele of the H-ras proto-oncogene VaII2 and a dominant-negative allele of the murine p53 tumor suppressor gene VaII35. Transformed cell lines were derived and found to be tumorigenic in syngeneic mice. Immunization with irradiated p53 + ras-transformed MEF, but not primary MEF or unrelated syngeneic cells, protected mice from subsequent challenge with live tumor cells. The role of different immune cell subsets in the effector phase of anti-tumor immunity induced by immunization with p53 + ras-transformed MEF was investigated by in vivo antibody depletion experiments. Immunized mice depleted of CD8+ T, NK or B cells were resistant, but depletion of CD4+ T cells rendered mice susceptible to tumorigenic challenge. In contrast to the tumor-specific immune responses mounted against most chemically or UV-induced tumors, a series of independently derived p53 + ras-transformed MEF were cross-reactive in tumor rejection assays. In addition, immunization with C3H-derived L-929 cell lines expressing single gene products H-ras or p53 did not protect mice against tumorigenic challenge with p53 + ras-transformed tumors. However, MEF transformed by expression of either H-ras or p53 were cross-protective in vivo. Our data suggest that the p53 + ras-transformed MEF share tumor rejection antigens which are also induced by single gene transformation of the parental primary cell but are not the products of oncogenic ras or p53 protein.
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PMID:Mouse embryo fibroblasts transformed by activated ras or dominant-negative p53 express cross-reactive tumor rejection antigens. 754 May 99


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