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)

The retinoblastoma sensitivity protein (Rb) and the p53 gene product both appear to function as negative regulators of cell division or abnormal cellular growth in some differentiated cell types. Several types of cancers have been shown to be derived from cells that have extensively mutated both alleles of one or both of these genes, resulting in a loss-of-function mutation. In the case of the p53 gene, this mutational process appears to occur in two steps, with the first mutation at the p53 locus resulting in a trans-dominant phenotype. The mutant p53 gene product enters into an oligomeric protein complex with the wild-type p53 protein derived from the other normal allele and such a complex is inactive or less efficient in its negative regulation of growth control. This intermediate stage of carcinogenesis selects for the proliferation of cells with one mutant allele, enhancing the probability of obtaining a cancer cell with both alleles damaged. The DNA tumor viruses have evolved mechanisms to interact with the Rb and p53 negative regulators of cellular growth in order to enhance their own replication in growing cells. SV40 and adenovirus type 5 produce viral encoded proteins that also form oligomeric protein complexes with p53 and Rb, presumably inactivating their functions. These viral proteins are also the oncogene products of these viruses. Thus, the mechanisms by which cancer may arise in a host, via mutations or virus infections, have fundamental common pathways effecting the same cellular genes and gene products; Rb and p53.
 ...
PMID:Tumor suppressor genes. 214 May 9

Mutant p53 can contribute to transformation, while wild-type (wt) p53 is not oncogenic and actually inhibits transformation. Furthermore, wt p53 may act as a suppressor gene in human carcinogenesis. We now describe the temperature-sensitive behavior of a particular mutant, p53val135. Like other p53 mutants, it can elicit transformation at 37.5 degrees C. However, at 32.5 degrees C it suppresses transformation, behaving like authentic wt p53. Moreover, the proliferation of transformed cells expressing p53val135 is dramatically inhibited at the permissive temperature. Significantly, the inhibition of both transformation and proliferation is reversible upon temperature upshift. These data demonstrate that the ability of wt p53 to suppress transformation is not due to a general lethal effect, but rather to a reversible growth arrest. p53val135 may prove instrumental for gaining insight into the cellular and molecular properties of wt p53.
 ...
PMID:Conditional inhibition of transformation and of cell proliferation by a temperature-sensitive mutant of p53. 214 98

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.
 ...
PMID:[Application of flow cytometry to the study of hematologic disorders: analysis of oncogene products]. 214 49

Remarkable advances in the understanding of specific inherited and acquired genetic events that are important in colonic carcinogenesis have occurred in the last several years. Studies of the population genetics of colon cancer have determined that the gene responsible for familial adenomatous polyposis (FAP), and Gardner's syndrome has been localized on the long arm of chromosome 5 and have more clearly defined the importance of genetic influences in 'sporadic' colon cancer. Studies of the molecular genetics of colon cancer have identified acquired alterations in oncogenes such as the K-ras gene and in putative tumor suppressor genes such as the FAP gene on chromosome 5, the p53 gene on chromosome 17, and the DCC gene on chromosome 18, which appear to mediate important steps in the adenoma-dysplasia-carcinoma sequence. Some of these research advances (FAP gene carriage) are already being used clinically to identify individuals at risk for colon cancer, and they offer great promise for the future of both prevention and therapeutic programs.
 ...
PMID:Lessons from the genetics of colon cancer. 217 30

This is a time of rapid progress in the field of human bronchogenic carcinogenesis due to recent advances in cellular and molecular biology. Important developments over the last 10 years include establishment of methods for culturing NHBE cells under defined conditions, and molecular biological and biochemical epidemiological techniques for identifying genetic changes that are associated with malignant transformation of these cells. Most progress in defining genes associated with human carcinogenesis has been due to discoveries related to oncogenes and more recently, tumor suppressor genes. As was described in Section II.B.3.a, we now know that oncogene products serve as growth factors, growth factor receptors, and cytosolic and nuclear regulatory proteins. In addition, although the actions of putative tumor suppressor genes are less well understood, the first isolated tumor suppressor gene Rb, interacts with the products of DNA viruses which, in turn, are involved in regulation of transcription as was described in Section II.B.3.b. Thus, not surprisingly, both oncogenes and tumor suppressor genes code for classes of proteins that are known to play an important role in regulation of cell proliferation. Recently, a second gene that appears to possess tumor suppression activity (p53) has been identified on the short arm of chromosome 17 (17p). The initial data suggesting a possible tumor suppressor gene on chromosome 17p came from cytogenetic and RFLP studies associating loss of heterozygosity in the chromosome 17p13 region with tumor cells and tissues. Since the p53 gene is located in this region it was evaluated and found to be frequently or always altered in several types of tumor cells. Recently, it was determined that introduction of the wild-type p53 gene into NIH3T3 cells will inhibit subsequent malignant transformation. Thus, the preponderance of evidence now supports the hypothesis that while mutated p53 acts as an oncogene, the wild-type p53 gene codes for a tumor suppressor function. The role of balance between oncogenes and tumor suppressor genes in control of proliferation is presently an active area of investigation. As discussed, introduction of a chromosome containing a tumor suppressor gene will suppress tumorigenicity of a malignant cell line, even though that cell line possesses an active c-Ha-ras oncogene. Whether or not the level of expression of an activated oncogene is related to tumorigenicity is presently being investigated.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Cellular and molecular biological aspects of human bronchogenic carcinogenesis. 219 49

To evaluate the role of p16 multiple tumor suppressor (MTS1) and p53 protein in human radiation-induced skin cancer, we examined the expression of p16 and p53 in eight cases using immunohistochemistry. An abnormal location of p16 expression in the cytoplasm was found in seven of eight cases, but the expression of p53 in nuclei was noted in only three of eight cases. These findings suggest that the inactivation of p16 might be related to its binding with another unknown oncoprotein in the cytoplasm and thus lead to carcinogenesis.
 ...
PMID:Abnormal location of p16 protein and overexpression of p53 protein in human radiation-induced skin cancer. 747 71

It has been reported that the p53 gene mediates an ionizing radiation-induced G1 arrest in mammalian cells. To further characterize this important phenomenon, a panel of seven human diploid fibroblast cell strains and 14 human tumor cell lines from a variety of sources with both wild-type and mutant p53 status were assayed for their susceptibility to G1 arrest after gamma-ray irradiation by a continuous labeling [3H]thymidine incorporation technique. An irreversible G1-block involving 20-70% of the cell population was observed in diploid fibroblasts irradiated with 4 Gy. The block was abolished by transfection with the Human Papilloma Virus E6 gene and in an ataxia telangiectasia (AT) cell line, indicating a role for the AT and p53 genes respectively in this process. In contrast to wild-type normal fibroblast cell strains, the G1-block in all tumor cell lines was significantly reduced, irrespective of their p53 status. None of the nine human tumor cell lines with mutant p53 genes showed a significant G1-block following irradiation with 4 Gy. Among the five tumor cell lines expressing wild-type p53, two showed no apparent G1-block. The remaining three showed a G1-block involving only 8-15% of the cell population, a block much smaller in magnitude than that seen in diploid fibroblasts. Finally, a diploid fibroblast cell strain and a tumor cell line, both showing a normal p53 and p21/WAF1 expression pattern, were examined for pRb phosphorylation before and after irradiation. The diploid fibroblast cell strain showed a significant G1-arrest and a clear inhibition of pRb phosphorylation by irradiation whereas the tumor cells showed no G1-arrest and no inhibition of pRb phosphorylation. These results suggest that (1) multiple genetic factors may modulate the occurrence and magnitude of the G1-arrest induced by exposure to ionizing radiation, (2) the capacity for p53 to mediate a radiation-induced G1 arrest is significantly reduced in tumor cells, (3) the disruption of G1-block modulating factor(s) other than p53 may be an important step in carcinogenesis.
 ...
PMID:Diminished capacity for p53 in mediating a radiation-induced G1 arrest in established human tumor cell lines. 747 18

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.
 ...
PMID:p53 overexpression in the multistep process of esophageal carcinogenesis. 750 63

While the life-extending and disease-modulating effects of caloric restriction (CR) are well documented in whole animal studies and in correlative experiments using cells taken from CR animals, very few studies have used cells in culture after their removal from the CR-fed animal. In using this in vivo-->in vitro approach we have attempted to examine the proposition that the effects of CR can be transferred to individual cells by analyzing the cellular functions of proliferation and transformation, the activation of oncogenes, and the methylation of DNA as a function only of diet. Pancreatic acinar cells excised from CR-fed Brown-Norway rats and placed in rich medium showed different responses compared to cells from ad libitum (AL)-fed controls. CR had the effect of slowing growth rate and protecting against spontaneous and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced transformation over 14 passages of cells in culture. At the molecular level, cells from the CR animals showed reduced c-Ha-ras oncogene expression and mutation as well as reduced mutation of the p53 suppressor gene. CR also increased genomic methylation of ras DNA. We conclude that the effects of CR treatment of the animal are transferred to individual cells and note that these responses (decreased proliferation and transformation; depressed oncogene expression and mutation and decreased suppressor gene mutation; and increased oncogene methylation) are cellular and molecular analogs of in vivo weight loss, life extension, and carcinogenesis modulation, which are hallmarks of CR in the whole animal. The fact that these responses are seen generations after the cells are removed from the CR-treated animal indicates that CR causes a permanent predisposition of pancreatic acinar cells to these modulated responses and shows the value of the in vivo-->in vitro protocol in studies that relate diet to cellular and molecular function.
 ...
PMID:Effects of caloric restriction in animals on cellular function, oncogene expression, and DNA methylation in vitro. 750 63

Cancers in which mutations have been identified in putative tumor suppressor genes, such as the TP53 gene, the retinoblastoma (RBI) gene, the adenomatous polyposis coli (APC) gene, and the Wilms tumor (WTI) gene, frequently show loss of the corresponding allele on the homologous chromosome. To identify locations of tumor suppressor genes involved in uterine cancer, we examined loss of heterozygosity (LOH) by using genomic probes detecting RFLPs in 35 uterine cancers at 29 loci throughout the genome, and with highly informative microsatellite markers in 21 uterine cancers at nine putative or known tumor suppressor gene loci. High frequencies of allelic loss found at loci on 3p (71%), 9q (38%), 10q (35%), and 17p (35%) suggest that tumor suppressor genes involved in uterine carcinogenesis exist in these regions. There were no significant differences in frequencies of LOH between cancers of the uterine cervix and cancers of the uterine endometrium at any of the loci tested.
 ...
PMID:Allelotype of uterine cancer by analysis of RFLP and microsatellite polymorphisms: frequent loss of heterozygosity on chromosome arms 3p, 9q, 10q, and 17p. 751 41


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