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 unique subline of BALB/c mice, designated "BALB/cV," exhibits an intermediate mammary tumor incidence (47%) and harbors a distinct milk-transmitted mouse mammary tumor virus (MMTV). Virus expression and virus-host interactions were examined during the different stages of mammary tumorigenesis (normal, preneoplastic, and neoplastic) in the BALB/cV system. Protein immunoblot analyses established the presence of correctly processed (BALB/cV)MMTV structural proteins in all types of BALB/cV mammary tissues. Competition enzyme-linked immunosorbent assays demonstrated that cells from each biologic phenotype were capable of supporting high levels of (BALB/cV)MMTV protein expression. However, mammary epithelial cells that spontaneously underwent the inappropriate pathway of squamous metaplasia did not contain detectable levels of (BALB/cV)MMTV structural proteins. Iodination experiments revealed the presence of a 68K env-related protein on the surface of BALB/cV mammary cells. Nevertheless, sera from 40 mice bearing BALB/cV-positive mammary tissues did not contain detectable levels of anti-env antibodies. Metabolic labeling experiments showed that the half-life of transformation-related, host cell protein p53 (approximately equal to 60 min) in the distinct BALB/cV mammary cell populations was similar to that reported for normal mouse 3T3 cells. It appears that p53 is not stabilized by protein interactions involving any MMTV-encoded or MMTV-induced protein in mammary tumor cells. These characteristics of the BALB/cV system are compatible with the hypothesis that MMTV is only one of two or more cooperating factors required to mediate complete mammary transformation.
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PMID:Mammary cancer stages in BALB/cV mice: mouse mammary tumor virus expression and virus-host interactions. 303 52

The protein p53 is highly expressed in a large variety of transformed cell types originating from diverse species. These include cells transformed by Simian virus 40 (SV40), adenovirus and Abelson virus, as well as a variety of chemically transformed cells. Substantial amounts of p53 are also present in certain non-transformed cells, for example, some embryonic tissues. The protein may be localized in different cellular compartments in normal and transformed cells. The strong correlation between tumorigenicity and high levels of p53 suggests an important role of p53 in tumorigenesis. We report here experiments in which we have co-transfected the murine cellular gene encoding for p53 with a ras gene into primary rat embryo fibroblasts. Our results indicate that the p53-encoding gene can play a causal role in the conversion of normal fibroblasts into tumorigenic cells.
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PMID:Cooperation between gene encoding p53 tumour antigen and ras in cellular transformation. 639 Feb 17

Oncogenesis is a process resulting from genetic events which cause loss of growth control or inhibition of appropriate cell death. The Bcl-XL protein is a recently discovered member of the bcl-2 family which has been shown to protect cells from some forms of programmed cell death, but has not yet been implicated in the genesis of human carcinomas. In this report we explore the role of Bcl-XL overexpression in protecting cancer cells from p53-mediated apoptosis. Increased levels of Bcl-XL were found in a subset of primary human breast carcinomas, as well as in the breast cancer line, T47D. T47D cells were then transfected with a temperature-sensitive mutant of the tumor suppressor p53 (p53ts). Although many tumor cell lines undergo apoptosis when p53 is expressed, the T47D transfectants remained viable at temperatures permitting wild-type p53 phenotype. This suggested that endogenous Bcl-XL could protect cancer cells from p53-mediated apoptosis. To test this hypothesis, murine erythroleukemia cells were transfected with bcl-XL and p53ts. While cell lines expressing p53 alone rapidly died, those cells co-expressing Bcl-XL survived. These results demonstrate that Bcl-XL is capable of protecting cells from p53-mediated apoptosis, and suggest a possible mechanism by which tumors expressing Bcl-XL are able to partly overcome the tumor suppressor functions of p53.
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PMID:Bcl-XL protects cancer cells from p53-mediated apoptosis. 747 61

Among the solid tumors of childhood and adolescence, osteosarcoma (OS) represents the most prominent example of efficient aggressive chemotherapy with secondary surgical therapy. A specific subclassification of the tumor is indispensable and must include recent results of cell biology. The co-distribution of different collagen types I-VI reflects the diverse differentiation of osteosarcoma cells, supporting the concept of a pluripotent mesenchymal cell to be the stem cell of the tumor. In contrast, osteonectin (SPARC) may not be considered as a reliable marker for osteosarcoma. The experience of special proteins being secreted by osteosarcoma cells is rather limited. Detailed molecular biological studies are still lacking. A loss of alleles on chromosome 17, particularly in the defined region 17p 13, can be observed in more than 75% of all OS, suggesting the contribution of a tumor suppressor gene, p53, located in that region. It is a 53 kd nucleophosphoprotein binding the major transforming protein, the large T antigen of Simian Virus 40. Immunohistological results showed positive staining with the antibody Pab 240 in 13 of 18 cases. In one osteoblastic OS, a novel splice mutation resulting in a fusing of exon 5 directly to exon 7 was detected. RB1 gene is also of major importance for the tumorigenesis of OS. The multidrug resistance (mdr) is associated with a membrane-bound channel-forming transport protein, the P-glycoprotein. It is a conserved plasma membrane component of about 170 kd. Both the human isoforms mdr 1 and mdr 3 are localised in the long arm of chromosome 7.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New aspects of cell biology in osteosarcoma. 747 79

The human hepatitis B virus (HBV) HBx protein is a small transcriptional activator that is essential for virus infection. HBx is thought to be involved in viral hepatocarcinogenesis because it promotes tumorigenesis in transgenic mice. HBx activates the RAS-RAF-mitogen-activated protein (MAP) kinase signaling cascade, through which it activates transcription factors AP-1 and NF-kappa B, and stimulates cell DNA synthesis. We show that HBx stimulates cell cycle progression, shortening the emergence of cells from quiescence (G0) and entry into S phase by at least 12 h, and accelerating transit through checkpoint controls at G0/G1 and G2/M. Compared with serum stimulation, HBx was found to strongly increase the rate and level of activation of the cyclin-dependent kinases CDK2 and CDC2, and their respective active association with cyclins E and A or cyclin B. HBx is also shown to override or greatly reduce serum dependence for cell cycle activation. Both HBx and serum were found to require activation of RAS to stimulate cell cycling, but only HBx could shorten checkpoint intervals. HBx therefore stimulates cell proliferation by activating RAS and a second unknown effector, which may be related to its reported ability to induce prolonged activation of JUN or to interact with cellular p53 protein. These data suggest a molecular mechanism by which HBx likely contributes to viral carcinogenesis. By deregulating checkpoint controls, HBx could participate in the selection of cells that are genetically unstable, some of which would accumulate unrepaired transforming mutations.
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PMID:Hepatitis B virus HBx protein deregulates cell cycle checkpoint controls. 747 68

The dbl oncogene, generated by the truncation of the amino-terminal portion of the proto-oncogene sequence, encodes a guanine-nucleotide-releasing factor. The transforming activity of this oncogene has never been demonstrated in vivo or in vitro except in the NIH 3T3 mouse fibroblast cell line. The expression of the proto-dbl transcript is confined to tissues and tumors of neuroectodermal derivation. Therefore, to study the transforming activity of the dbl oncogene in vivo, we have generated transgenic mice that express this oncogene in neuroepithelial tissues. Mice carrying the dbl oncogene did not develop a tumor. Successively, to establish whether dbl interacts with the tumor suppressor gene p53 in tumorigenesis, we have used a p53 deficient mouse strain. The results reported here indicate that dbl is capable of causing tumor formation in vivo when its expression is driven in an appropriate cellular and genetic environment.
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PMID:Dbl expression driven by the neuron specific enolase promoter induces tumor formation in transgenic mice with a p53(+/-) genetic background. 748 91

Recent in-vitro models of mammary epithelial cell (MEC) immortalization have provided a practical approach to begin to dissect the molecular mechanisms of breast tumorigenesis. Introduction of a single oncogene, the human papilloma virus (HPV)-16 E6, induces efficient and reproducible preneoplastic transformation of normal MECs, by inducing degradation of the tumor suppressor protein p53. The role of p53 has also been demonstrated by analyses of a model of gamma-radiation-induced MEC transformation. Recently, efficient retroviral gene transfer has allowed identification of multiple mammary epithelial cell types that show distinct susceptibilities to HPV E6 and E7 oncogenes, indicating a cell-type-specific predominance of the tumor suppressor proteins p53 and Rb which are targeted by E6 and E7, respectively. Further analyses of these models are likely to elucidate the biochemical mechanisms of early mammary tumorigenesis.
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PMID:Preneoplastic transformation of human mammary epithelial cells. 749 87

The timing of p53 mutation in the multistep process of esophageal carcinogenesis is still under debate. We tested p53 expression in 16 samples of low-grade and 29 samples of high-grade esophageal dysplasia (ED) coexisting with esophageal squamous cancer (ESC) in 31 patients who underwent total esophagectomy. In normal mucosa, a positive immunoreaction was detected in 10 of 31 cases, always restricted to the lower half of the epithelial thickness. We detected p53-positive nuclei in 11 of 16, 23 of 29, and 23 of 31 samples of low-grade ED, high-grade ED, and ESC, respectively. Cases exhibiting positive staining in dysplastic samples also demonstrated positive immunoreaction in the carcinomatous tissue. Immunoreactivity in cancer cells was never found in the absence of positive dysplastic nuclei. A significantly higher score of immunoreactive nuclei was detected in high-grade versus low-grade and in low-grade compared with normal mucosa. These data suggest that p53 mutation may represent an early event in esophageal oncogenesis.
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PMID:p53 overexpression in the multistep process of esophageal carcinogenesis. 750 63

The causative factors leading to breast cancer are largely unknown. Increased incidence of breast cancer following diagnostic or therapeutic radiation suggests that radiation may contribute to mammary oncogenesis. This report describes the in vitro neoplastic transformation of a normal human mammary epithelial cell strain, 76N, by fractionated gamma-irradiation at a clinically used dose (30 Gy). The transformed cells (76R-30) were immortal, had reduced growth factor requirements, and produced tumors in nude mice. Remarkably, the 76R-30 cells completely lacked the p53 tumor suppressor protein. Loss of p53 was due to deletion of the gene on one allele and a 26-bp deletion within the third intron on the second allele which resulted in abnormal splicing out of either the third or fourth exon from the mRNA. PCR with a mutation-specific primer showed that intron 3 mutation was present in irradiated cells before selection for immortal phenotype. 76R-30 cells did not exhibit G1 arrest in response to radiation, indicating a loss of p53-mediated function. Expression of the wild-type p53 gene in 76R-30 cells led to their growth inhibition. Thus, loss of p53 protein appears to have contributed to neoplastic transformation of these cells. This unique model should facilitate analyses of molecular mechanisms of radiation-induced breast cancer and allow identification of p53-regulated cellular genes in breast cells.
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PMID:Loss of p53 protein during radiation transformation of primary human mammary epithelial cells. 751 Dec 7

The mutational spectrum for the TP53 gene was investigated in a large series of bladder tumors and bladder tumor cell lines. Tumors and cell lines were screened for the presence of TP53 point mutations by single-strand conformational polymorphism analysis followed by direct sequencing. Mutations were detected in 16 of 88 (18%) tumors and 4 of 14 cell lines (28%). In total, twelve missense mutations, one nonsense mutation, three deletions, and two insertions were identified by direct sequencing. Of the thirteen point mutations sequenced, only one was a transition at a CpG site, whereas five G:C-->T:A transversions were found, suggesting a major role for exogenous mutagens in bladder tumorigenesis. Tumors were also examined for loss of heterozygosity (LOH) on chromosome arm 17p. LOH of one or more markers on 17p was detected in 31% of tumors. All eight tumors with a TP53 mutation from patients informative at TP53 had LOH, whereas nine tumors with LOH at TP53 did not have an identified mutation. Three tumors had LOH on 17p at sites distal to the TP53 locus but retained both TP53 alleles, suggesting the involvement of another tumor suppressor gene on 17p in bladder tumorigenesis in some tumors.
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PMID:The spectrum of TP53 mutations in bladder carcinoma. 751 40


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