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

Chronically immunosuppressed individuals are susceptible to lymphoreticular tumors. Up to 15% of patients with congenital deficiencies such as ataxia=telangiectasia may develop malignancies, mainly high-grade B cell non=Hodgkin's lymphomas (NHLs). AIDS lymphomas are comprised of NHLs including Burkitt's lymphoma (BL) and primary cerebral lymphomas (PCLs). Almost 3% of all AIDS patients (2824 of 97,258 cases) developed NHL. Epstein-Barr virus (EBV) as a co-factor in AIDS lymphomagenesis has been studied: in 12 cases of 24 AIDS lymphomas EBV by DNA in situ hybridization was found. In an analysis of 6 primary cerebral lymphomas, .5 were positive for EBV DNA by Southern blotting. In Burkitt's lymphoma the characteristic genetic alteration affects the c-myc oncogene. In 1/3 of BL p53 mutations were found but none in the 43 NHLs suggesting that p53 mutations and c-myc activation act synergistically in the pathogenesis of these tumors. Cytotoxic agents dideoxyinosine, dideoxycytosine, and zidovudine may cause secondary neoplasia. 8 of 55 AIDS patients under zidovudine treatment developed high-grade lymphoma 23.8 months subsequently; recently doses were reduced. PCL was found in 21 of 90 patients. A 5.2 months survival was associated with combined treatment with cyclophosphamide, Oncovin (vincristine), methotrexate, etoposide, and cytosine arabinoside compared with 11.3 months with chemotherapy. Colony-stimulating factors (CSFs) alleviate drug-induced myelotoxicity and zidovudine-induced neutropenia, however, l8 of 11 patients receiving granulocyte-macrophage CSF developed hematological toxicity. Interleukine-2 produced by T-helper cells enhancing tumor cells cytotoxicity has been used in AIDS-associated cryptosporidial diarrhea and in 4 patients with AIDS lymphoma with modest response, but its stimulation of the HIV-infected substrate may increase viral proliferation.
 ...
PMID:AIDS lymphomas. 161 63

Mouse 10T1/2 cells were transfected with combinations of T24 H-ras, human c-myc and the proline 193 mutant form of p53. The three-gene ras/myc/p53 combination was significantly more efficient than single genes or double gene combinations in inducing transformed foci in vitro. An analysis of cell lines isolated after transfections with ras, ras/myc, ras/p53 and ras/myc/p53 indicated that the last combination contained significantly higher levels of ras protein than the other combinations, produced tumors in syngeneic mice with a shorter latency period, and exhibited an increased ability to form lung tumors in an in vivo experimental metastasis assay. Synergistic interactions between ras, myc and mutant p53 genes were observed in focus formation and metastasis assays, suggesting that the action of the three oncogenes in malignant transformation occurs along separate but interactive pathways. These results support a working model of oncogene cooperativity in which alterations in myc and p53 permit elevated expression of ras, which is important in a mechanism affecting both cellular transformation in vitro and tumor dissemination in vivo.
 ...
PMID:Evidence for synergistic interactions between ras, myc and a mutant form of p53 in cellular transformation and tumor dissemination. 162 May 51

During post-lactational mammary gland involution, the bulk of mammary epithelium dies and is reabsorbed. This massive cell death and tissue restructuring was found to be accompanied by a specific pattern of gene expression. Northern blot analysis showed that weaning resulted in a dramatic drop in ODC, a gene involved in synthesis of a component of milk, and the nearly simultaneous induction of SGP-2, a gene associated with apoptotic cell death. These changes were followed by decreases in expression of milk protein genes to basal levels and expression of genes associated with regulation of cell proliferation and differentiation, p53, c-myc and TGF-beta 1. Subsequently, additional genes implicated in stress response, tissue remodelling, and apoptotic cell death were transiently expressed, expression peaking at about 6 days post-weaning. A non-random degradation of DNA yielding the oligonucleosomal length fragmentation pattern typical of apoptotic cell death (Wyllie, 1980; Wyllie et al., 1980) was detected in association with morphological changes and gene expression. The correlations between: (a) changes in morphology, (b) pattern of gene expression and (c) changes in DNA integrity suggest that complementary programs for cell death and tissue remodelling direct post-lactational mammary gland involution.
 ...
PMID:Apoptotic cell death and tissue remodelling during mouse mammary gland involution. 163 91

We have examined a series of squamous cell carcinomas (SCC) of the anus, anal intraepithelial neoplasia grade III (AINII) lesions and haemorrhoids for the presence of sequences from transforming human papillomavirus (HPV) types by polymerase chain reaction (PCR)/Southern blotting. In addition, the same DNAs have been analysed for abnormalities in the c-myc, p53 and retinoblastoma (Rb-1) gene loci by Southern blotting. HPV16 sequences were detected in a total of 38 of 50 (76%) and HPV18 sequences in 4 of the 50 cancers (8%). Of 12 haemorrhoids examined, none contained HPV16 or HPV18 sequences. Amplification of c-myc was demonstrated in 15 of the 50 cancers (30%), of which 13 were HPV16 positive, and one also positive for HPV18. Amplification of c-myc was not observed in the 5 AINIII or any of the 41 haemorrhoid DNAs analysed. Rearrangement of c-myc was not seen in any of the DNAs. Gross rearrangement, or loss of p53 or Rb-1 loci was not observed in any normal or tumor tissue. However, in preliminary analysis of p53 sequence, three tumours negative for HPV were heterozygous for p53 point mutation whereas six HPV positive tumours and two haemorrhoids were wild-type sequence throughout exons four to ten.
 ...
PMID:Status of c-myc, p53 and retinoblastoma genes in human papillomavirus positive and negative squamous cell carcinomas of the anus. 165 Apr 45

Recent advances in understanding the molecular etiology of colorectal carcinoma have made possible a discussion of molecular targets for therapy of the disease. The genes for two inherited predispositions, familial adenomatous polyposis and the Lynch syndrome, have been mapped to specific chromosomal locations. At least five of the genes that are altered in structure or expression to give rise to the tumorigenic phenotype have been isolated by molecular cloning: The K-ras and N-ras protooncogenes have been shown to be altered by point mutation, and expression of the c-myc protooncogene is deregulated. The p53 and DCC genes, both tumor suppressor genes or antioncogenes, are deleted or altered so as to be rendered nonfunctional. Although a single tumor may not suffer all these changes, available evidence indicates that most colorectal tumors contain at least one of these alterations. In addition, work in cell culture and animal systems indicates that tumor cells may be converted to nonmalignant cells by reversing the effects of just one of these changes.
 ...
PMID:Are there molecular targets for therapy of colon cancer? 166 28

Malignant gliomas and medulloblastomas which are the most common primary malignant brain tumours of adult and children, respectively, resemble other neurogenic tumours as they frequently contain gene amplification and show non-random loss of specific chromosomal regions. In gliomas the gene which is most often amplified, is the epidermal growth factor receptor gene. In many cases the gene is rearranged as well, producing abnormally small epidermal growth factor receptor proteins. More than 80% of tumours have lost chromosome 10 and losses of 9p13, 17p and 22 occur in subgroups of cases. 17p loss is associated with point mutations of the p53 gene, but the relevant genes in the other chromosomal regions remain to be identified. For medulloblastoma the most frequent chromosomal abnormality is i(17q). Whether or not p53 gene mutations are the targets of 17p losses in these tumours remains to be determined. Approximately 5% of medulloblastoma biopsies contain gene amplification, although the incidence in medulloblastoma cell lines is more than 80%. c-myc is the gene which is most frequently amplified in this tumour type. The relationship of these various molecular genetic abnormalities to the biology of the tumours and the course of the patients remains largely unexplored.
 ...
PMID:Cytogenetics and molecular genetics of malignant gliomas and medulloblastoma. 166 88

The MDA-468 human breast cancer cell line displays the unusual phenomenon of growth inhibition in response to pharmacological concentrations of EGF. This study was initiated with the objective of elucidating the cellular mechanisms involved in EGF-induced growth inhibition. Following EGF treatment the percentage of MDA-468 cells in G1 phase increased, together with a concomitant depletion in S and G2/M phase populations, as revealed by flow cytometry of DNA content. The apparent G1 block in the cell cycle was confirmed by treating the cells with vinblastine. DNA synthesis was reduced to about 35% of that measured in control, untreated cells after 48 h of EGF treatment, as measured by the incorporation of [3H]thymidine. DNA synthesis returned to normal following the removal of EGF from the growth-arrested cells. In order to locate the EGF-induced event responsible for the G1 arrest more precisely, we examined the expression of certain cell cycle-dependent genes by Northern blot analysis. EGF treatment did not alter either the induction of the early G1 marker, c-myc, or the expression of the late G1 markers, proliferating cell nuclear antigen, and thymidine kinase. However, EGF-treated cells revealed down regulation of p53 and histone 3.2 expression, which are expressed at the G1/S boundary and in S phase, respectively. These results indicate that EGF-induced growth inhibition in MDA-468 human breast cancer cells is characterized by a reversible cell cycle block at the G1/S boundary.
 ...
PMID:EGF-dependent growth inhibition in MDA-468 human breast cancer cells is characterized by late G1 arrest and altered gene expression. 167 99

The expression of nine proto-oncogenes (c-myc, N-myc, c-fos, c-jun, p53, H-ras, N-ras, c-raf, hst) and other three genes (AFP, PCNA, GST-P) were investigated during spontaneous development to hepatocellular carcinomas (HCCs) in LEC rats. Expressions of c-myc, H-ras, N-ras, c-raf, p53, and PCNA genes were detected but did not significantly change during the development to HCCs in LEC rats. Expressions of N-myc, hst, and AFP genes were not detectable since 5 weeks after birth. Expression of c-fos gene was detected in one out of four HCCs. Significantly increased expression of c-jun gene was observed in the liver tissues of LEC rats aged 8 months. The high expression was decreased in HCCs. On the other hand, the expression of GST-P gene increased in parallel with the clinical course of the development to HCCs in LEC rats. The increased expression of GST-P gene was observed in the liver tissues of LEC rats aged 8 months, and HCCs showed very high expression of GST-P gene. These observations suggest that both c-jun and GST-P genes may play a role in the spontaneous development to HCCs in LEC rats.
 ...
PMID:[A study on expression of various oncogenes and tumor-associated genes in LEC rats spontaneously developing hepatitis and hepatoma]. 169 10

The molecular genetics of melanoma is little understood and has concentrated largely on DNA analyses. We have examined mRNA levels of 21 different oncogenes, antioncogenes, growth factors and proteases in cultured melanocytes and 17 melanoma cell lines. C-mel, c-erb-B2, c-myc, c-src-1, p53, platelet derived growth factor A chain, gro, transforming growth factor alpha, epidermal growth factor receptor and tissue plasminogen activator were all expressed in at least some cell lines. Most striking was the finding that there are significant intercorrelations of c-myc, p53 and c-src-1 levels, and between p53 and c-erb-B2, which may be due to common regulatory control of these genes in cells of the melanocytic lineage.
 ...
PMID:Gene expression in melanoma cell lines and cultured melanocytes: correlation between levels of c-src-1, c-myc and p53. 169 9

The murine B-cell hybridoma B9 requires interleukin-6 (IL-6) for its survival and proliferation in vitro. We show here that withdrawal of IL-6 from B9 cultures results in programmed death, concomitant with arrest of the cells in the G1 phase of the cell cycle. Unlike several other systems that undergo programmed cell death, no induction of transcripts corresponding to the testosterone-repressed message-2 or transglutaminase genes is observed during this process. Upon readdition of IL-6 to G1-arrested B9 cells, viability is maintained and entry into S phase occurs after a lag period of 10 to 12 hr. Northern blot analysis showed that the immediate-early mRNAs normally induced shortly after growth factor stimulation in quiescent fibroblasts (c-fos, c-jun, Egr-1, c-myc, JE, and KC), and other growth-related genes (2F1, c-Ha-ras, and p53), are either not induced or remain unchanged during G1 to S phase progression. A correlation was found, however, between the temporal pattern of expression of several G1/S phase genes (dihydrofolate reductase, thymidine kinase, transferrin receptor, and histone H3) and DNA synthesis. These results demonstrate that IL-6-induced viability and growth of hybridoma (and, presumably, plasmacytoma) cells is mediated via novel signal transduction pathways.
 ...
PMID:Suppression of programmed death and G1 arrest in B-cell hybridomas by interleukin-6 is not accompanied by altered expression of immediate early response genes. 170 72


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>