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)

Previously we had identified a p53 DNA-binding motif in the 5' region of the CK8 gene This finding led us to study the role of p53 protein in the regulation of CK8 gene expression and its role in tumorigenesis. Human lung cancer cell lines stably transfected with antisense p53 cDNA that expressed little p53 protein were analyzed. CK8 mRNA and the protein expression in these p53 antisense clones were very low as revealed by northern and western blot analysis. Immunofluorescence studies indicated that the cytokeratin networks around the nuclei of these cells collapsed; although some staining was observed around the nuclei. Antisense clones were highly invasive on in vitro matrigel assay. Scanning electron microscopy of the surface topography of these antisense clones revealed a large number of microvilli on their surfaces, a phenotype characteristic of tumor cell invasion. These findings suggest that functional inactivation p53 protein could be an important step in tumor progression.
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PMID:Functional inactivation of p53 by antisense RNA induces invasive ability of lung carcinoma cells and downregulates cytokeratin synthesis. 871 87

Hepatocellular carcinoma (HCC) is a heterogeneous disease. HCC derived from different stages of cellular differentiation may have different clinical and pathobiological behavior. To test the hypothesis that HCC can be classified into two types based on its phenotypic markers (hepatocellular and biliary differentiation), liver tissues from 290 Chinese patients with HCC were studied. Expression of hepatocytic differentiation marker (HEP-PAR-reactive antigen), biliary differentiation markers (AE1-AE3, cytokeratin-19), proliferation markers (Ki-67, proliferating cell nuclear antigen), alpha-fetoprotein, p53, and transforming growth factor-alpha in the tumor tissue were assessed by immunohistochemistry. Hepatocytic differentiation marker was detected in 99.7% and biliary differentiation markers were detected in 29.3% of these tumors. Clinically, no patient with HCC with biliary markers survived for more than 27 weeks compared with a 22.6% survival rate in patients with HCC negative for biliary markers. HCCs positive for the biliary differentiation markers showed features of more aggressive disease in terms of poorer cellular differentiation (P < 0.001) and high-level expression of proliferation markers (Ki-67, P < 0.001; proliferating cell nuclear antigen, P = 0.0114) compared with HCCs without biliary markers. HCCs with biliary markers also had a higher level of expression of alpha-fetoprotein (P < 0.001) and p53 (P = 0.0077). Classification of HCCs based on its phenotypic (differentiation) markers has both clinical and pathobiological implications.
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PMID:Classification of hepatocellular carcinoma according to hepatocellular and biliary differentiation markers. Clinical and biological implications. 886 66

Ninety-four cases of early abortion have been studied. Five histological groups of lesion have been identified by routine histological techniques on abortion materials, group I corresponding to partial hydatidiform mole. Cytogenetic analyses have revealed chromosome anomalies in near 50% of cases with a prevalence of triploidies followed by trisomies and monosomies. Normal histological findings are more often associated with normal karyotypes and group I with abnormal karyotypes but a specific correlation between histological pattern and cytogenetic anomalies is lacking. Neither some histochemical reactions nor the well preserved immunohistochemical reactivities of beta-hCG, hPL, PLAP, AFP, cytokeratin, vimentin, desmin, factor VIII, CD 68, MIB1 (growth fraction), EGF-R, p53 and c-erbB-2 oncoproteins have disclosed specific chromosome anomalies. They have only allowed a better definition of histological groups. A simple histological evaluation, although extended to immunohistochemical reaction may not substitute the cytogenetic analyses, not even for purposes of preselection.
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PMID:[Correlation of the histological and cytogenetic pictures in placental tissue from early abortion. Does immunohistochemistry have a role?]. 900 96

Activation by point mutation of ras family genes as well as point mutations of the p53 tumor suppressor gene are found in many tumors. Here we describe a rare case of malignant neuroendocrine pancreatic tumor with multiple metastases in different organs showing strong positivity for synaptophysin, glucagon-like peptide 1, pan-cytokeratin, moderate positivity for chromogranin, Phe-5 and calcitonin and weak positivity for vasointestinal peptide. We found a point mutation at codon 61 of the c-N-ras oncogene, and point mutations in the p53 tumor suppressor gene in the primary tumor as well as in its metastases in liver. The mutation in the c-N-ras gene was a cytosine to adenine transversion, resulting in the amino-acid lysine. Allele specific hybridization showed that the mutation involved one of two c-N-ras alleles as the oligonucleotide for the normal codon also hybridized to amplified tumor DNA. Concomitant mutation of the p53 tumor suppressor gene at codons 248 and 249 was found. The mutation in codon 248 was a cytosine to guanine transversion resulting in the amino-acid glycine. The mutation in codon 249 was a third base, G- > T, transversion leading to a change from arginine to serine. This is the first time that concomitant point mutations in c-N-ras and p53 have been found in a neuroendocrine pancreatic tumor. Based upon these and our previous results, we concluded that these genetic changes may play a role in the development of this particular pancreatic tumor.
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PMID:Concomitant point mutation of tumor suppressor gene p53 and oncogene c-N-ras in malignant neuroendocrine pancreatic tumor. 904 54

Merkel cell carcinoma is a very rare tumor. This is why it is not known whether this neoplasm behaves differently in the vulvar location than at other sites. We present a patient with a Merkel cell carcinoma assessed with a light optical microscope, immunohistochemistry, and electron microscope. Only eight previous cases have been reported in the literature. We discuss pathologic findings, such as histologic trabecular pattern under the optical microscope and neurosecretory granules (similar to Merkel cell carcinoma of the skin) under the electron microscope. Also discussed are the results of immunohistochemistry for low-molecular-weight cytokeratin, neuron-specific enolase, chromogranin, and Leu 7, and molecular study of N-ras, K-ras, N-myc, and p53 genes. Little is known about Merkel cell carcinoma of the vulva, but it seems to have a more aggressive behavior and poorer prognosis than Merkel cell carcinoma at other sites.
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PMID:Merkel cell carcinoma of the vulva. 906 65

A case of carcinosarcoma composed of both adenocarcinoma and sarcomatous elements in the non-trigone region of the urinary bladder is presented. The epithelial element was a well to poorly differentiated adenocarcinoma with focal squamous metaplasia. The sarcomatous elements disclosed spindle cell sarcoma with focal epithelioid pattern and myxoid change in the stroma, together with chondrosarcomatous and rhabdomyosarcomatous elements. By immunohistochemical examination, not only the carcinoma element but also the sarcomatous elements showed a positive immunoreaction for cytokeratin (CK), epithelial membrane antigen (EMA) and carcinoembryonic antigen. Some population of sarcomatous elements expressed smooth muscle actin and muscle specific actin (MSA) and a limited portion of epithelioid area showed a positive immunoreaction for desmin, MSA and myoglobin, indicating leiomyosarcomatous and rhabdomyosarcomatous differentiation, respectively. Unexpectedly, tumor cells in the chondrosarcomatous element revealed a simultaneous positivity of CK and EMA as well as S-100 protein. Both epithelial and sarcomatous elements showed an intensive positive immunoreaction for p53 and heat shock protein (HSP) 70. However, HSP27 and HSP60 were detected in most epithelial elements and only in a small number of tumor cells in the sarcomatous area. These findings indicate that sarcomatous elements, including heterologous elements, may derive from epithelial elements with partial or complete loss of epithelial features, and different factors other than p53 and HSP70 may associate with the morphological alteration of carcinoma.
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PMID:Carcinosarcoma of the urinary bladder: expression of epithelial markers and different expression of heat shock proteins between epithelial and sarcomatous elements. 908 35

Animal models have an important role in cutaneous research. The guinea pig has proven to be a useful model in a wide spectrum of these cutaneous studies; however, its usefulness is often compromised by the need for depilation. A euthymic hairless guinea pig (HGP) model avoids the problems associated with depilation. Morphologically, as in human skin, these animals have a multi-cell-layer epidermis. Proliferation kinetic studies, as well as documentation of the degree of immunologic cross-reactivity between available antibodies to human cutaneous antigens, could extend the usefulness of this animal model. We performed a battery of anti-human antibodies on formalin fixed tissue, to a variety of antigens present within the skin and on inflammatory cells. These included CD3, UCHL-1, OPD4, L-26, KP-1, Factor XIIIa, S-100 protein, cytokeratin (AE1, AE3 and CK1), CAM 5.2, vimentin, CD 34, Factor VIII, fibronectin, SM actin, collagen IV, laminin, Bcl-2, p53, Ki-67, and PCNA. Cross-reacting antibodies included: CD3, S-100 protein, cytokeratin (AE1, AE3 and CK1), vimentin, Factor VIII, SM actin, collagen IV, p53, Ki-67, and PCNA. Although this battery of antibodies is limited, the markedly increased staining of Ki-67 and PCNA within keratinocytes in the epidermis as compared to normal human skin reflects a high proliferative rate. In addition, positive staining for p53, Ki-67, and PCNA may be useful in studying effects on cell cycle kinetics and apoptosis.
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PMID:Evaluation of cross-reacting anti-human antibodies in the euthymic hairless guinea pig model (HGP) suggests that the HGP may be a model for the study of proliferative skin disease. 913 82

To examine the differentiation and proliferative activity of tumor cells, 30 osteosarcomas, including osteoblastic, chondroblastic, fibroblastic, malignant fibrous histiocytoma-like, telangiectatic, giant cell-rich low-grade central, and epithelioid types, were studied immunohistochemically. A variable number of tumor cells in all cases showed osteocalcin immunoreactivity. In four preparations of the frozen sections, osteoblastic, fibroblastic, and chondroblastic tumor cells were positive for bone-type alkaline phosphatase antibody 2D3. S-100 protein immunoreactivity was found not only in seven tumors of the chondroblastic type, but also in four of nine osteoblastic tumors and each of the low-grade central, giant cell-rich, and epithelioid types. A histiocytic marker, CD68, was negative for tumor cells in all cases. Some cells of 17 tumors were positive for desmin and/or alpha-smooth muscle actin; this was regarded as an indication of myofibroblastic differentiation. Tumor cells of the epithelioid type and those of two osteoblastic tumors expressed cytokeratin (CAM5.2) and epithelial membrane antigen. Proliferating-cell nuclear antigen (PCNA) reactivity was found in the cell nuclei of 22 tumors, most of which were high grade. Many cells in six high-grade tumors also showed the nuclear staining for p53 protein. Of these tumors, PCNA and p53 positivities tended to be more numerous in osteoblastic cells, atypical spindle-shaped, and bizarre giant cells than in well-developed chondroid cells. From these findings, osteosarcomas are concluded to be composed basically of osteoblastic cells, that are indispensable for diagnosis of osteosarcomas, with a variable number of chondroblastic, myofibroblastic, and, rarely, epithelioid cells, and this manifold cellular differentiation corresponds to the histological and clinical diversities. The osteoblastic, fibro- or myofibroblastic, and undifferentiated cells mainly participate in proliferation of osteosarcomas. The p53 gene alterations may play a part in the neoplastic transformation and proliferation of osteosarcomas.
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PMID:Histological and immunohistochemical diversities, and proliferative activity and grading in osteosarcomas. 916 46

P53 is overexpressed in more than 50% of all human cancers. A previous study suggested that p53 was also overexpressed in oral papillomas. This study was carried out to investigate whether p53 expression was correlated with expression of the cellular proliferation marker Ki-67 and the epithelial differentiation marker cytokeratin-4 (CK4) in oral papillomas. Formalin-fixed paraffin-embedded sections of 30 oral papilloma specimens and 30 unmatched normal oral mucosal specimens were processed for immunohistochemistry, using an avidin-biotin-peroxidase procedure and monoclonal antibodies. A semiquantification analysis on p53 and Ki-67 labeling indices was performed. Twenty-eight of 30 (93%) papilloma specimens were positive for p53. The percentage of p53-positive cells in the basal layer was 60.4 +/- 14.8 (mean +/- SD, n = 28), and that of Ki-67-positive cells was 26.7 +/- 14.4. There was no correlation between expression of p53 and that of Ki-67. Expression of CK4 was inversely correlated with the expression of Ki-67 but not correlated with the expression of p53.
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PMID:Expression of p53, Ki-67 and cytokeratin-4 (CK4) in oral papillomas. 917 72

A cell line was established from a mixed mullerian tumor of the ovary and designated LN1. Histopathologic analysis of the fresh tumor specimen demonstrated a highly aneuploid heterologous tumor comprised of undifferentiated mesodermal components with carcinomatous cells present as a smaller population. Long-term in vitro culture resulted in the establishment of a cell line that exhibits an epithelial-like morphology and expresses epithelial antigens cytokeratin, epithelial membrane antigen, and carcinoma antigen TAG-72. These cells also express mesenchymal intermediate filaments, vimentin, and desmin. Karyotypic analysis revealed a basic triploid pattern with multiple chromosomal abnormalities, most notably an isochromosome of the short arm of five present in three copies. Analysis of oncogene expression revealed that LN1 cells constitutively express mRNA for c-ras, c-erbB2, and p53. The expression of mRNA for cellular oncogenes correlated with the presence of corresponding oncoproteins, p21H-ras, p21K-ras, and p185erB2 and mutant p53 protein. In summary, coexpression of epithelial and mesenchymal antigens by LN1 cells lends support to the hypothesis that epithelial and mesenchymal elements comprising mixed mullerian tumors of the ovary are derived from a common stem cell precursor. Furthermore, this cell line represents a functional in vitro model to evaluate the biologic activities of these unusual and highly aggressive ovarian malignancies.
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PMID:Cytogenetic, morphologic and oncogene analysis of a cell line derived from a heterologous mixed mullerian tumor of the ovary. 919 89


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