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)

A common site of ecotropic murine leukemia virus integration designated Evi-2 (ecotropic viral integration site-2) has been identified in BXH-2 myeloid tumors. As part of experiments to determine whether Evi-2 identified a new proto-oncogene locus involved in myeloid disease, we determined its chromosomal location. We mapped Evi-2 to mouse Chromosome 11 using standard recombinant inbred strain and genetic backcross analysis. We then determined the location of Evi-2 relative to other proto-oncogene and growth factor loci located on Chromosome 11 by interspecific backcross analysis. The loci included in this study were the proto-oncogene loci, Erbb, Erba, and Rel, as well as, Il-3 (interleukin-3), Csfgm (granulocyte-macrophage colony stimulating factor), and Trp53-1 (transforming protein p53). All loci except Erbb had been previously mapped to Chromosome 11 with the use of somatic cell hybrids and consequently their positions on Chromosome 11 were not known. One proto-oncogene, Erbb-2 (analogous to the neu proto-oncogene), and one growth factor locus, Csfg (granulocyte colony-stimulating factor), which had not been mapped in the mouse were also localized on Chromosome 11 using the interspecific backcross mice. Recombination between Evi-2 and all proto-oncogene and growth factor loci was demonstrated, suggesting that Evi-2 may ultimately identify a new proto-oncogene involved in myeloid disease. This study revealed a number of interesting conserved linkage groups common to mouse and man.
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PMID:Localization of Evi-2 to chromosome 11: linkage to other proto-oncogene and growth factor loci using interspecific backcross mice. 285 Nov 24

Steady-state levels of myc, fos, p53, sis, and neu mRNAs were measured in eight variants derived from the Dunning R3327 rat prostate adenocarcinoma and compared to levels in normal dorsal prostate. Expression of the myb and erbB oncogenes in the Dunning tumors was below the limits of detection. Myc, p53, and sis mRNA levels in all tumors were at or above control levels. Fos mRNA levels were below control levels in four of five anaplastic tumors and were above control levels in the remaining tumors. A comparison of mRNA levels along the two Dunning lineages revealed that increased expression of these oncogenes did not correlate with tumor progression.
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PMID:Oncogene expression in prostate cancer: Dunning R3327 rat dorsal prostatic adenocarcinoma system. 321 75

We investigated alterations in the structure and expression of oncogenes in mammary tumors and mammary tumor-derived cell lines. In 16 of 95 samples, we detected amplification of the human neu oncogene, also known as c-erB-2, accompanied by overexpression in the tumors from which intact RNA could be isolated. In 10 of these DNAs, the linked oncogene c-erbA was also amplified, whereas another gene on human chromosome 17, p53, was present in normal copy numbers. Overexpression of c-erbA could not be detected in the tumors analyzed. The relatively high frequency of neu amplification points to a functional role in human breast cancer. Coamplification of the c-erbA oncogene could contribute to this disease as well but is most likely fortuitous.
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PMID:Amplification of the neu (c-erbB-2) oncogene in human mammmary tumors is relatively frequent and is often accompanied by amplification of the linked c-erbA oncogene. 329 59

The development of effective screening tests for colorectal tumors is essential given the high frequency of these cancers in the general population, and more especially in various groups at risk. Sporadic and hereditary colorectal cancers result from the accumulation of mutations in oncogenes, such as ras, myc, neu/HER2, and in tumor suppressor genes such as apc, dcc, p53. The detection of ras or p53 mutations in DNA extracted from stool has been shown to be feasible and might be useful for the development of new screening tests. Many mutations in these genes can also be used as new prognostic factors. Identification of mutation in the apc gene responsible for familial polyposis, or its indirect detection through the study of polymorphism in such families, is completely changing the previously recommended medical attitude for the screening of this disease, and therefore may decrease or even avoid major medical follow-up. These changes are also true for the nonpolyposis hereditary colorectal tumors, also called Lynch syndrome, since the responsible hMSH2, hMLH1, hPMS1 and hPMS2 genes have recently been cloned. Mutations in these genes do not seem to be limited to families with Lynch syndrome, and could account for a predisposition of some patients to develop colorectal or other tumors.
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PMID:Contribution of molecular oncology in the detection of colorectal carcinomas. 749 39

The results of conventional treatments for lung cancer remain poor and long-term survival rates have changed little over the last 10 years. In the same period of time there has been an explosion in the knowledge on the processes of cellular transformation, tumour progression, invasion and metastasis. The major categories of biological events implicated in non-small cell lung cancer include growth factor receptors expression (epidermal growth receptor, p185c-neu), autocrine growth factor production (transforming growth factor alpha), dominant oncogenes activation (ras genes) and deletion of tumour suppressor genes (p53 gene, retinoblastoma gene) and these are some of the abnormalities associated with specific histological types and with poor prognosis. Additional prognostic information can be obtained from the evaluation of the ploidy and proliferative activity of the tumours, carbohydrate antigens expression, presence of neuroendocrine differentiation and the evaluation of markers of the sequential steps involved in the process of tumour dissemination.
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PMID:Biological prognostic factors in non-small cell lung cancer. 755 21

The retinoblastoma (RB) tumour suppressor gene has been associated not only with retinoblastoma but also with several other tumours like osteosarcoma, small cell lung carcinoma and prostate and breast cancer. We have studied the incidence of RB gene alterations in 96 primary breast tumours using Southern blotting techniques. The outcome has been related with patient and tumour characteristics, oncogene amplifications, p53 mutations and prognosis. RB gene alterations were found to occur more frequently in estrogen receptor (ER)-positive than in ER-negative tumours and less frequently in tumours with oncogene amplification than in tumours without oncogene amplification of HER2/neu, c-myc or 11q13. RB gene alteration was observed in tumours both with and without a p53 gene mutation. Data on 87 patients (mean age, 59.6 years; median follow-up, 108 months) and RB gene alterations revealed a significant association between the frequency of RB gene alterations and node-negative patients (p < 0.01) or smaller (< 2 cm) tumours (p < 0.01), but no relation with age, differentiation grade or (relapse-free) survival. Patients with and without RB gene alterations showed the same relapse-free and overall survival.
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PMID:Association between RB-1 gene alterations and factors of favourable prognosis in human breast cancer, without effect on survival. 761 56

P44 Ro (Mel) is a human malignant melanoma cell line derived from a testicular metastasis in a DNA repair deficient, xeroderma pigmentosum patient. This line harbors a N-ras gene mutated in codon 61. To investigate other cellular genes possibly contributing to the expression of its transformed phenotype, four XP44 revertant cell lines were isolated by different selection procedures and the association of the level of expression of various oncogenes (including N-ras) and tumor suppressor genes with the selection for the revertant phenotype was determined. The revertants exhibited a significant but variable degree of phenotypic reversion, according to the selective pressure to which they were submitted, and a phenotypic stability dependent on their constant maintenance in selective medium. Back-revertant lines were isolated by culturing revertant lines in control medium for several weeks. The comparison between parental, revertant and back-revertant cells has revealed that, beyond the mutation in codon 61 of N-ras, two groups of genes appear to be also implicated in the transformation process of XP44 RO (Mel) cells: one group, comprising pim A, trk, Rb and p53, whose expression is independent of the cell selection conditions; the other group, comprising Ha-ras, N-ras, neu 1, fos and met H, whose expression is more or less dependent upon such conditions. The myc gene is apparently not involved in this phenomenon. These results, besides strengthening the concept that carcinogenesis is a multigenic process, suggest that diverse mechanisms can lead to the transformed phenotype, but that these mechanisms might have some pathway(s) in common.
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PMID:Cellular genes possibly involved in the transformation process of the human melanoma cell line XP44 RO (Mel). 765

Benign breast disease (BBD) is a heterogeneous group of benign breast problems that has been associated with breast cancer risk by several investigators. Genetic alterations have been described in breast carcinomas under the headings of loss of heterozygosity (1p, 3p, 7q, 11p, 17p, 17 and 18q), mutations (p53, c-H-ras-1), and/or gene amplifications (c-myc, int-2/FGF3, and c-erbB-2/neu). In an attempt to determine whether these genetic alterations might also be involved in the development of BBD, we have analyzed such alterations in 50 BBD lesions. The histological types of samples studied were: 37 fibroadenomas; 8 benign phyllode tumors; and 5 fibrocytic diseases. Cellular DNA was extracted from tissues and from corresponding blood leukocytes according to standard techniques, digested with appropriate restriction endonucleases, and analyzed by Southern blot. The following are informative cases found in a total number of patients analyzed for each locus: 13 of 26 for L-myc (1p); 9 of 23 for THRB (3p); 11 of 29 for met (7q); 27 of 50 for c-H-ras-1 (11p); 3 of 13 for TP53 (17p); 14 of 50 for D17S30 (17p); 20 of 33 for D17S4 (17q); and 13 of 33 for D18S5 (18q). No loss of heterozygosity was detected at any of the examined loci. Alternatively, none of the 50 BBD cases displayed an amplification of the three genes tested (c-myc, int-2/FGF3, and c-erbB-2/neu). Our results show that molecular alterations, which are more frequently involved in malignant breast carcinomas, do not occur in BBD lesions. These results indicate that these molecular alterations could constitute late events in the pathogenesis of breast carcinomas.
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PMID:Benign breast disease: absence of genetic alterations at several loci implicated in breast cancer malignancy. 767 Dec 54

We introduce a new epithelial ovarian carcinoma cell line (UCI 107) from a patient with papillary adenocarcinoma of the ovary who had not been previously treated. The growth characteristics, chemosensitivity, tumorgenicity, cytogenetics, antigen expression, and receptor status were examined. A standardized photometric assay was implemented to determine the response to single drug agents including doxorubicin (ADR), cisplatin (CDDP), and Taxol. Tumorgenicity was determined utilizing female athymic mice implanted either subcutaneously (sc) or intraperitoneally (ip) with 1 x 10(7) UCI 107 cells. UCI 107 cells grow rapidly in culture with lag phase of approximately 48 hr, population doubling time of 24-36 hr, and saturation density of 4.8 x 10(5) cells/cm2. The 50% inhibitory concentration values for the chemotherapeutic agents were 0.170, 0.029, and 0.330 microM for ADR, Taxol, and CDDP, respectively. Nude mice produced ip tumors within 15 days, resulting in death from carcinomatosis 40-45 days postimplantation. Subcutaneous tumor nodules (100 mm3) were observed in nude mice 12-13 days post-tumor implantation reaching a maximum tumor volume of approximately 10,000 mm3 by Day 30. The cytogenetic composite karyotype is as follows: 46, X, der (X) t (X;7) (p11;q22), inv dup (1) (q12;q32), t (6;6;11;22) (p21.3;q16;q23.3;q13.3), del (13) (q14.1). The cell line expresses progesterone receptor, increased levels of p53 protein, and cytokeratins. It does not appear to express Her-2/neu protein, estrogen receptor, nor the CA 125 tumor marker. In conclusion, UCI 107 displays unique cellular properties which make it an attractive model for the study of ovarian cancer.
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PMID:Characterization and development of UCI 107, a primary human ovarian carcinoma cell line. 767 98

The expression of 6 different oncoproteins and 2 tumour suppressor gene products in the plasma cells of 63 bone marrow samples was used to determine a profile of the oncogenic phenotype of patients with multiple myeloma. Dual label flow cytometry after periodatelysine paraformaldehyde fixation was used to detect cell surface phenotype and intracellular protein expression simultaneously. The normal range for both the incidence and intensity of expression was determined for each protein by analysing plasma cells (high CD38 intensity) in 22 normal bone marrow samples. The percentage of myeloma patients with a greater than normal incidence of plasma cells expressing these proteins was 53% for c-myc, 28% for Rb, 28% for bcl-2, 27% for c-fos, 24% for p53 wild, 22% for p53 mutant, 13% for c-neu and 13% for pan-ras. When a panel of 8 antibodies was used, 82% of the samples (n = 28) had an increased incidence of expression by at least one oncoprotein or tumour suppressor gene product. The 5 patients with a normal incidence of expression of all 8 proteins were in plateau stage and 4 had not received chemotherapy for more than 12 months. The number of patients with an increased incidence of expression by 2 or more oncoproteins was significantly greater (X2 = 9.0; p < 0.005) in progressive disease (55%) than in stable disease (14%) but there was no specific phenotype pattern associated with progressive disease. All 6 oncoproteins and both tumour suppressor gene products had a greater incidence and intensity of expression in progressive than in stable disease. The expression of c-myc oncoprotein correlated with c-myc mRNA expression in the same samples (n = 10) but c-myc did not correlate with either the plasma cell labelling index (r = -0.15) nor serum thymidine kinase (r = 0.10). Our results suggest that there is a heterogeneous, non-systematic but almost universal presence of activated oncogenes and tumour suppressor genes in the plasma cells of patients with multiple myeloma and that disease progression is associated with the accumulation of a variety of secondary genetic changes which confer increased malignant behaviour.
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PMID:The oncoprotein phenotype of plasma cells from patients with multiple myeloma. 769 21


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