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)

We present a cytogenetic and fluorescence in situ hybridization (FISH) study, using centromeric probes for chromosomes 3, 7, 11, and 18, TP53 gene (17p13), and RB-1 locus (13q14) DNA probes, in four cases of plasma cell leukemia (PCL). Among the four cases, three presented monosomy of the RB-1 locus and one monoallelic deletion of the TP53 gene. The present report shows the usefulness of the FISH technique to detect abnormalities not previously observed by conventional cytogenetics.
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PMID:Cytogenetic and fluorescence in situ hybridization studies in four cases of plasma cell leukemia. 1106 1

To study genetic changes associated with the development of breast cancer and the extent of its hereditary predisposition, paraffin-embedded tissue samples were obtained from monozygotic twin pairs concordant for breast cancer through the linked Swedish Twin and Cancer Registries. DNA samples extracted from the matched tumour and normal tissues of nine twin pairs were analysed for allelic imbalance using a series of microsatellite markers on chromosomes 13 and 17, containing loci with known tumour suppressor genes. Multiple losses of constitutional heterozygosity (LOH), consistent with a loss of large genomic region, the whole chromosome or chromosome arm, was found in at least three pairs of twins. One double mitotic crossover was identified in one tumour sample in a pair concordant for LOH at multiple loci on both chromosomes. Recombination breakpoints were mapped to regions delineated by D13S218 and D13S263, and D13S155 and D13S279, respectively. In general, no genetic effect of losing the same allele within a twin pair was found. However, for one marker at chromosome 13 (D13S328, between the BRCA2 and the RB-1 loci) and two markers on chromosome 17 (D17S786, distal to the p53 locus, and D17S855, an intragenic BRCA1 marker) the proportion of twin pairs with the same LOH was significantly higher than expected. These regions may reflect hereditary genomic changes in our sample set. In addition, tumour DNA samples from a subset of 12 twin pairs were analysed for BRCA1 and BRCA2 mutations using exon-by-exon single-strand conformation polymorphism analysis. Two unclassified BRCA2 variants, with a putative pathogenic effect, were identified, but no pathogenic alterations were found in the BRCA1 gene.
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PMID:Allelic imbalance on chromosomes 13 and 17 and mutation analysis of BRCA1 and BRCA2 genes in monozygotic twins concordant for breast cancer. 1115 37

Molecular and kinetic analyses have contributed to our understanding of the biology of transitional cell carcinomas (TCC) of the bladder. The concordant pattern of X-chromosome inactivation of multiple TCCs appearing at different times and at different sites and concordant genetic abnormalities in a subset of muscle-invasive TCC strongly support a monoclonal origin and a homogeneous tumor cell selection throughout the neoplasm. However, topographic intratumor heterogeneity results from the accumulation of genetic lesions in tumor suppressor genes, predominantly neurofibromatosis (NF)-1-defective in the superficial compartment and tumor protein p53 (TP53)-defective in the deep one, with lower proliferation and down-regulation of apoptosis in the latter. TCCs follow the general concept of multistep carcinogenesis and proceed through two distinct genetic pathways responsible for generating different TCC morphologies. These are the inactivation of cyclin-dependent kinase inhibitors (p15, p16, and p21WAF/CIP1) in low-grade TCC and early TP53-mediated abnormalities in high-grade TCC. TCC progression correlates with genetic instability and accumulation of collaborative genetic lesions mainly involving TP53, retinoblastoma (RB)-1, and growth factors. Distinctive genetic (low incidence of RB-1 and NF-1 abnormalities) and kinetic (slower cell turnover) profiles also correlate with a "single-file" infiltration pattern and poor survival in muscle-invasive TCCs. The underlying molecular changes of carcinoma in situ involve multiple and more extensive deletions (normally TP53-defective) than coexistent invasive TCC, suggesting an independent genetic evolution, while low-grade dysplasia is mainly polyclonal and shows a low rate of gene deletions.
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PMID:Molecular and kinetic features of transitional cell carcinomas of the bladder: biological and clinical implications. 1131 26

Hepatocellular carcinoma (HCC) is one of the most frequent-occurring malignant tumours worldwide, but molecular changes of tumour DNA, with the exception of viral integrations and p53 mutations, are poorly understood. In order to search for common macro-imbalances of genomic tumour DNA, 21 HCCs and 3 HCC-cell lines were characterized by comparative genomic hybridization (CGH), subsequent database analyses and in selected cases by fluorescence in situ hybridization (FISH). Chromosomal subregions of 1q, 8q, 17q and 20q showed frequent gains of genomic material, while losses were most prevalent in subregions of 4q, 6q, 13q and 16q. Deleted regions encompass tumour suppressor genes, like RB-1 and the cadherin gene cluster, some of them previously identified as potential target genes in HCC development. Several potential growth- or transformation-promoting genes located in chromosomal subregions showed frequent gains of genomic material. The present study provides a basis for further genomic and expression analyses in HCCs and in addition suggests chromosome 4q to carry a so far unidentified tumour suppressor gene relevant for HCC development.
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PMID:Frequent genomic imbalances suggest commonly altered tumour genes in human hepatocarcinogenesis. 1153 Dec 55

The Retinoblastoma (Rb-1) and p53 genes appear to play an important role in controlling cell division, and mutations in Rb-1 and p53 have been reported widely in non-gynecological cancers. Unlike other cancer-related genes, which become activated during carcinogenesis, it is the loss of wild type p53 and Retinoblastoma protein (RB) function that is thought to contribute to cancer development. These genes therefore, have been called tumor suppressor genes since normal function appears to be necessary for negative control of cell growth. Several viral oncoproteins have been shown to interact with RB and p53. It seems likely that the formation of these complexes inactivates the cellular protein resulting in an overall effect similar to somatic mutation of the Rb-1 or p53 genes. The HPV16 transforming proteins E7 and E6 complex with protein products of Rb-1 and p53, respectively. In HPV positive anal and cervical tumors the normal function of RB and p53 may be inhibited by these viral proteins and so mutation within the RB-1 and p53 gene coding sequences would not appear to be a necessary step in the genesis of these tumors. However, in HPV negative tumors from the same tissues, loss of wild type Rb-1 and p53 activity may only be achieved by somatic mutation of these genes.
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PMID:Tumor suppressor genes: new pathways in gynecological cancer. 1157 29

The ovarian corpus luteum plays a critical role in reproduction being the primary source of circulating progesterone. After ovulation the corpus luteum is build by avascular granulosa lutein cells through rapid vascularization regulated by gonadotropic hormones. The present study was performed to investigate whether this process might be influenced by the human chorionic gonadotropin (hCG)-dependent expression of different tumor suppressor genes and hypoxia dependent transcription factors. RNA was isolated from cultured granulosa lutein cells, transcribed into cDNA, and the transcript level of following genes were determined: RB-1, VHL, NF-1, NF-2, Wt-1, p53, APC, and hypoxia inducible factor-1 (HIF-1), -2, and -3alpha. Additionally, the influence of hCG on the expression of VHL, p53, and HIf2alpha were investigated. We demonstrate that in human granulosa lutein cells the tumor suppressor genes RB-1, VHL, NF-1, NF-2, Wt-1, p53, and APC and the hypoxia dependent transcription factors HIF-1alpha, -2alpha, and -3alpha are expressed. In addition, we showed that hCG regulates the expression of p53, VHL, and HIF-2alpha. Our results indicate that hCG may determine the growth and development of the corpus luteum by mediating hypoxic and apoptotic pathways in human granulosa lutein cells.
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PMID:Chorionic gonadotropin regulates the transcript level of VHL, p53, and HIF-2alpha in human granulosa lutein cells. 1545 16

Multiple myeloma (MM) is a malignancy of differentiated B lymphocytes and has remained an incurable disease. Chromosomal abnormalities are among the most important prognostic parameters for MM. Cytoplasm immunoglobulin-enhanced interphase fluorescent in situ hybridization (FISH) has been a standard cell-targeting method for identifying genomic aberrations in MM. We have developed another cell-targeting approach by using CD138 magnetic microbeads to sort plasma cells for FISH analysis. The FISH panel consisted of four probes targeting RB-1, D13S319, immunoglobulin H, and p53 loci. We reviewed the FISH and conventional cytogenetic results of 60 patients with MM. The present cell-targeting approach in conjunction with the FISH probe panel was more sensitive than FISH performed on untargeted cells in detecting prognostically significant genomic aberrations (72 versus 24%, P = 0.0016). The frequencies of genomic abnormalities identified were similar to previously reported data obtained with the standard cell-targeting method. Therefore, our cell-targeting approach and FISH panel reliably detect prognostically important genomic abnormalities in MM and are potentially suitable for widespread use.
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PMID:A practical approach to the detection of prognostically significant genomic aberrations in multiple myeloma. 1625 53

Copper toxicity associated with Wilson's disease is known to cause neuronal damage and death in the basal ganglia and frontal cortex leading to Parkinson-like symptoms and cognitive deficits. Our previous work in cultured human NTERA-2-N neurons showed that copper-induced neuronal apoptosis is dependent on the induction and nuclear translocation of the tumor suppressor protein, p53. Because p53 acts as a DNA-binding transcription factor, this work used an oligonucleotide array to identify p53 target genes that are differentially regulated in copper-loaded neurons. Arrays representing 145 human genes expressed downstream of p53 were hybridized with labeled mRNA from control and copper-treated neurons. Differentially regulated mRNAs included those involved in the regulation of the cell cycle, cytoprotective mechanisms, and apoptotic mechanisms. Transfection of cells with a dominant-negative p53 construct enabled us to determine which molecular events were dependent on p53 expression. Copper treatment resulted in the upregulation of p21, reprimo, stathmin, and Tp53INP1, all known to participate in cell cycle arrest. Protective mechanisms included the upregulation of stat-3, and the heat-shock proteins, heat-shock protein (Hsp) 70 and Hsp 27. Both p53-dependent and -independent mechanisms leading to apoptosis were identified including insulin-like growth factor binding protein-6, glutathione peroxidase, bcl-2, RB-1, PUMA, and several members of the redox active PIG family of proteins. Thus it appears that following copper-mediated neuronal DNA damage, the regulation of a variety of pro- and antiapoptotic genes are responsible for determining neuronal fate.
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PMID:Expression profiling of p53-target genes in copper-mediated neuronal apoptosis. 1639 88

Uterine carcinosarcoma (malignant mixed Mullerian tumor) is an uncommon female genital tract neoplasm characterized by an admixture of epithelial and stromal malignant cells. We report a case of 50-year-old peri-menopausal woman diagnosed to have early-stage (IB due to FIGO) uterine carcinosarcoma of the homologous type with superficial (3mm) myo-invasion. The patient showed no clinical symptoms of the disease and had no family history of female genital tract malignancies. Positive immunostaining for steroid receptors (estrogen-alpha and progesterone receptors), cytokeratin, and EGFR was detected only in the carcinomatous area, whereas beta-catenin, BCL-2, COX-2, p16(INK4a), PTEN, RB-1, and vimentin were immunoreactive in both components. Androgen receptor, CD10, desmin, HER-2/neu, and P53 were found to be negative either in the carcinomatous or in the sarcomatous area. Tumor proliferative activity was higher in the carcinomatous (25%) than in the sarcomatous (2%) component. Based on these findings, immunohistochemical evaluation of multiple receptor status in the carcinomatous and sarcomatous areas of carcinosarcoma may provide a clue to the pathogenesis and hormonal receptor status of this uncommon uterine malignancy.
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PMID:Immunohistochemical analysis of carcinomatous and sarcomatous components in the uterine carcinosarcoma: a case report. 1820 53

Mutation of the RB-1 and p53 tumor suppressors is associated with the development of human osteosarcoma. With the goal of generating a mouse model of this disease, we used conditional and transgenic mouse strains to inactivate Rb and/or p53 specifically in osteoblast precursors. The resulting Rb;p53 double mutant (DKO) animals are viable but develop early onset osteosarcomas with complete penetrance. These tumors display many of the characteristics of human osteosarcomas, including being highly metastatic. We established cell lines from the DKO osteosarcomas to further investigate their properties. These immortalized cell lines are highly proliferative and they retain their tumorigenic potential, as judged by their ability to form metastatic tumors in immunocompromised mice. Moreover, they can be induced to differentiate and, depending on the inductive signal, will adopt either the osteogenic or adipogenic fate. Consistent with this multipotency, a significant portion of these tumor cells express Sca-1, a marker that is typically associated with stem cells/uncommitted progenitors. By assaying sorted cells in transplant assays, we demonstrate that the tumorigenicity of the osteosarcoma cell lines correlates with the presence of the Sca-1 marker. Finally, we show that loss of Rb and p53 in Sca-1-positive mesenchymal stem/progenitor cells is sufficient to yield transformed cells that can initiate osteosarcoma formation in vivo.
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PMID:Metastatic osteosarcoma induced by inactivation of Rb and p53 in the osteoblast lineage. 1869 45


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