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)

C3H mouse embryo cells, which normally have low inherent spontaneous transformation, underwent malignant transformation while chronically infected with Mycoplasma fermentans or Mycoplasma penetrans. This mycoplasma-mediated oncogenic process had long latency (more than 7 weeks of persistent mycoplasmal infection) and showed multistage progression characterized by reversibility and irreversibility of malignant properties upon removal of M. fermentans from culture. Marked expression of H-ras and c-myc mRNA, but not N-myc, src, N-ras, or p53 mRNA, was found in the mycoplasma-transformed C3H cells that exhibited characteristic malignant properties of morphological changes and uncontrolled cell growth. However, at least up to the eleventh week of persistent mycoplasma infection, the marked expression of H-ras or c-myc mRNA in C3H cells depended on continued presence of the mycoplasma in culture. H-ras or c-myc mRNA rapidly declined to the undetectable low levels of nontransformed parental C3H cells, and all malignant properties of the once-fully-transformed C3H cells quickly reversed, if M. fermentans was eradicated from culture. In comparison, infection with M. penetrans for 7 or 11 weeks also induced a high level of H-ras, but not c-myc, mRNA expression in C3H cells. Despite having prominent amount of steady-state H-ras mRNA, these M. penetrans-infected C3H cells did not show any sign of malignant transformation. Thus, marked expression of H-ras gene alone was not sufficient to effect transformation in C3H cells. Interestingly, after a further prolonged (18 weeks) infection with either M. fermentans or M. penetrans, C3H cells revealed prominent chromosomal changes, expressed constitutively (with or without the presence of the transforming mycoplasmas) at high levels of both H-ras and c-myc mRNA and became permanently transformed. These cells were able to form tumors in animals.
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PMID:High-level expression of H-ras and c-myc oncogenes in mycoplasma-mediated malignant cell transformation. 911 27

Mutations of the N-ras oncogene and p53 tumor suppressor gene were simultaneously investigated in bone marrow cells from 44 patients with myelodysplastic syndrome (MDS) or MDS-derived leukemia by single-strand conformation polymorphism (SSCP) analysis followed by direct sequencing. The mutations of the N-ras gene were detected only in two cases with MDS-derived leukemia. Three patients with MDS-derived leukemia and one with refractory anemia with excess of blasts exhibited five mutations of the p53 gene. No concomitant mutations of both genes were observed in our study, suggesting that alterations of both genes could play an important role in the progression of MDS in a non-cooperative manner.
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PMID:No concomitant occurrence of the N-ras and p53 gene mutations in myelodysplastic syndromes. 917 41

The incidence of point mutations of H-, K- and N-ras and p53 oncogenes in male BALB/c mouse stomach tumors induced with N-methyl-N-nitrosourea (MNU) was examined by direct sequencing and PCR single-strand conformation polymorphism (PCR-SSCP). A mutation of GGT to AGT at K-ras codon 12 was found by SSCP in one adenocarcinoma from a total of 19 specimens including 5 adenocarcinomas, 9 adenomatous hyperplastic regions, 1 squamous cell carcinoma and 4 normal-like stomach regions from 4 mice. No mutations were detected by direct sequencing of H-, K- and N-ras oncogenes at exons 1 (codons 12 and 13) and 2 (codon 61) in a total of 26 specimens comprising 10 adenocarcinomas, 10 adenomatous hyperplastic regions, 2 squamous cell carcinomas and 4 normal-like stomach regions from 6 mice. No mutations were detected by direct sequencing of p53 oncogene at exons 5, 6, 7 and 8 in a total of 30 specimens including 13 adenocarcinomas, 8 adenomatous hyperplastic regions, 2 squamous cell carcinomas, 1 papilloma and 6 normal-like stomach regions from 7 mice. These results suggest that ras and p53 oncogenes do not play a role in mouse stomach carcinogenesis induced by MNU.
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PMID:Rare occurrence of ras and p53 gene mutations in mouse stomach tumors induced by N-methyl-N-nitrosourea. 919 27

Mutations of p53 and ras genes were analyzed in 40 and 31 1,3-butadiene (BD)-induced lymphomas of B6C3F1 mice (BLFs), respectively, and in 63 2',3'-dideoxycytidine-induced lymphomas, which were collected from B6C3F1 (n = 16) or NIH Swiss mice (DLSs; n = 47). The frequencies of K- and N-ras mutations in BLFs (32 and 13%, respectively) were higher than those in DLSs (13 and 2%, respectively). Seven of 10 K-ras-mutated BLFs contained codon 13 CGC mutations, whereas no mutation in K-ras codon 13 was detected in DLSs, suggesting that the codon 13 CGC mutation is specific for BD exposure. Interestingly, 8 of 13 BLFs with ras mutations were from low-dose (< or = 200 ppm) or stop-exposure (26 weeks) groups. These results suggest that ras mutations play an important role in the development of BD-induced lymphoma and may represent an early event. Analysis of genetic alterations in exons 5-8 of the p53 gene revealed mutations in seven of the BLFs and three of the DLSs. All seven BLFs carrying p53 mutations were collected from the high-dose (625 ppm) continuous exposure group, which might indicate that p53 is involved in the progression of BD-induced lymphoma and in late stage of lymphomagenesis. Mutations in ras and p53 genes are relatively infrequent in 2',3'-dideoxycytidine-induced lymphomas, suggesting that other genes must be involved.
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PMID:Genetic alterations of p53 and ras genes in 1,3-butadiene- and 2',3'-dideoxycytidine-induced lymphomas. 920 81

During the past years advances have been made in the understanding of the molecular mechanisms involved in the initiation and progression of thyroid carcinoma. Mutations in tumor suppressor genes such as p53 and oncogenes such as N-ras may be important for progression of well-differentiated thyroid carcinomas. Activation of the ret protooncogene located on chromosomal region 10q11.2 has been identified as a key factor in the initiation of papillary and medullary carcinoma. Integration of these discoveries into a prognostic classification scheme may allow us to better predict the biologic behavior of tumors in individual patients. Despite the recent advances in our understanding of the molecular events occurring during thyroid carcinogenesis, major questions persist regarding aspects of patient management. New diagnostic modalities may enable us to noninvasively discriminate between benign and malignant thyroid nodules, and to detect recurrent disease earlier. Although the optimal surgical procedure for well-encapsulated tumors is still debated, recent clinical studies have shown that for those patients with tumors > 1.5 cm, the routine use of RAI and hormone suppression can improve local control and survival rates. Findings in two recent reviews suggest that patients with widely invasive thyroid masses benefit from the surgical removal of all gross tumor. Further investigation is required to define the role of adjuvant radiotherapy and the most appropriate management of unresectable disease. Incorporation of prognostic markers into clinical staging systems should allow surgeons to better tailor their treatment plans for each patient. Translation of recent basic science advances into the clinical arena may also aid in the development of novel treatment strategies for patients with aggressive tumors.
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PMID:Thyroid carcinoma. 936 82

Occupational exposure to gasoline has been identified in several studies as a risk factor for renal-cell cancer. Cases of renal-cell cancer with and without work-related exposure to gasoline or gasoline and diesel fuel were studied for the presence of mutations in the tumour-suppressor gene p53 (n = 23 exposed and 30 non-exposed cases studied) and ras oncogene (n = 30 exposed and 36 non-exposed cases studied). An average cumulative exposure was estimated at 10 ppm-years benzene among the exposed. Three p53 mutations were detected by denaturing-gradient gel electrophoresis (DGGE) among the 23 exposed cases (3/23, 13%). Of the non-exposed referent cases, 4 had a mutation (4/30, 13%). All but one of the cases with a p53 mutation had smoked. A ras gene (K-ras or N-ras) mutation was found in 3 (3/66, 4.5%) cases, all of whom were smoker referents. We conclude that p53 and ras mutations are infrequent in renal-cell cancer associated with occupational exposure to gasoline. However, the majority of the mutations (6/7 for p53, and 3/3 for ras genes) were seen in smokers.
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PMID:Molecular analysis of occupational cancer: infrequent p53 and ras mutations in renal-cell cancer in workers exposed to gasoline. 938 61

Abnormal expression of SCL (TAL-1/TCL5) occurs in the majority of paediatric cases of acute T-cell lymphoblastic leukemia (T-ALL). Unexpectedly however, transgenic mice carrying scl coupled to the human T-cell specific CD2 enhancer (CD2-scl) did not spontaneously develop T-cell lymphomas despite high levels of scl expression in their thymocytes. Analogous to other transgenic models of lymphomagenesis, it is likely that additional genetic abnormalities are required to cooperate with scl to trigger lymphomagenesis. Two possible candidates are the p53 and N-ras genes which are mutated in some cases of T-ALL, particularly in relapsed disease. Therefore, we examined lymphomagenesis in the progeny of CD2-scl mice crossed with N-ras transgenic mice or p53 deficient. Surprisingly, the frequency of lymphomas in the p53 nullizygous or N-ras transgenic mice was not enhanced by expression of the scl transgene. In fact, expression of scl in both genetic backgrounds paradoxically reduced the frequency of thymic lymphomas and, at least in the p53 nullizygous mice, shifted the pattern of organ involvement to the peripheral lymphoid organs. In contrast, CD2-scl transgene expression accelerated lymphomagenesis in p53 heterozygous mice. These data suggest that the collaborative effects of scl with N-ras or p53 vary according to the developmental stage of the T-cell.
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PMID:The CD2-scl transgene alters the phenotype and frequency of T-lymphomas in N-ras transgenic or p53 deficient mice. 941 41

In vivo investigation of onco or suppressor genes may provide new information concerning chemical carcinogenesis. In earlier studies we illustrated the carcinogenic potential of COPP chemotherapeutical protocol in "long term" experiments. Elevated expression of oncogenes was shown as soon as 24 hours after treatment in CBA/Ca inbred mice, in "short term" experiments. Now we present the results of the follow-up study dealing with the carcinogenic effect of COPP. The genes most frequently involved were N-ras and p53, with the thymus being the target organ of COPP.
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PMID:In vivo effects of COPP protocol on onco- and suppressor gene expression in a 'follow up study'. 942 43

Several novel differentiated cell lines have been derived from a human hepatocarcinoma named HBG. Analysis of their functional properties evidenced a gradual differentiation process as they became confluent and a remarkable stability of the whole quiescent population for at least 6 weeks. However, when replated at low density after several weeks of quiescence, the differentiated cells were able to rapidly reverse to active proliferation, accompanied by transient dedifferentiation. Demonstration that the differentiated hepatic cells were growth-arrested in G1 phase was provided by the increased number of cells with 2C DNA content and decreased expression of S-phase markers. Characteristic features of oncogenes and cell cycle genes were defined during the differentiation process: (a) a biphasic expression of c-myc, with the latter wave covering the quiescence period; (b) opposite kinetics of c-Ki-ras and of N-ras expression with a pattern of changes paralleling that of c-myc; and (c) a decrease of cyclin D1 protein expression and of the cyclin D1-associated kinase activity. The mechanisms by which quiescent differentiated cells might reinitiate active proliferation were analyzed by studying several genes involved in cell growth and death regulation. We found: (a) a point mutation and loss of the specific activity of the tumor suppressor gene p53 without alteration of the apoptotic response to transforming growth factor beta1; (b) a gradual decrease of retinoblastoma protein, which was constantly present, mainly in a hyperphosphorylated form; and (c) an increase of cyclin-dependent kinase inhibitor p27 expression in confluent differentiating cells, as expected, whereas, surprisingly, a disappearance of the p21 protein was observed in parallel. These data may reflect specific mechanisms of cell cycle regulation in liver parenchymal cells through which these cells can proceed to control their reversible differentiation program.
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PMID:Cell cycle gene regulation in reversibly differentiated new human hepatoma cell lines. 948 53

The atomic bombing of Hiroshima and Nagasaki and the nuclear accident at Chernobyl raised the question of prenatal sensitivity to ionizing radiation-induced cancer. In this study, mice were exposed to single doses of gamma-radiation (0.2-2.0 Gy) at different embryonic stages. The tumor incidence increased with dose from 15% in control mice to 35% in mice irradiated with 2.0 Gy on 18 d of prenatal life. Various oncogenic events were investigated in lymphoid, liver, lung, and uterine tumors. We observed threefold to fivefold increases in myc expression in 25% of the lymphomas, and the expression of Ha-ras and p53 genes decreased in 40% and 60% of the lung tumors by twofold to fivefold. Point mutations were tissue specific: Ha-ras codon 61 mutations were found in about 40% of the liver adenocarcinomas, Ki-ras codon 12 mutations in about 17% of lung tumors, and p53 mutations in about 15% of the lymphomas. Amplification and rearrangement of the p53, myc, and Ha-, Ki- and N-ras genes were not detected. Loss of heterozygosity on chromosome 4 at the multiple tumor suppressor 1 and 2 genes was observed in all types of malignancies. Allelic losses on chromosome 11 at the p53 locus were found in lymphoid, liver, and lung tumors, but they were absent from uterine tumors. Multiple oncogenic changes were often detected. The frequency of carcinogenic alterations was similar in spontaneous and radiation-induced lymphoid, liver, and uterine tumors. In radiation-induced lung adenocarcinomas, however, the incidences of many oncogenic changes were different from those found in their spontaneous counterparts. This suggests that different oncogenic pathways are activated during spontaneous and in utero gamma-radiation-induced murine lung carcinogenesis.
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PMID:Carcinogenic alterations in murine liver, lung, and uterine tumors induced by in utero exposure to ionizing radiation. 949 10


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