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 investigated the expression of the tumour-suppressor and cell cycle control protein p53 in human first trimester and term placenta, three choriocarcinoma cell lines (Jeg-3, JAR, BeWo) and human choriocarcinoma. Using monoclonal antibodies against p53 (DO-7, Ab-6, DO-1, PAb 1801), paraffin-embedded sections of first trimester and full-term placentae, human choriocarcinoma and Jeg-3, JAR and BeWo, as well as cytospins, were evaluated immunohistochemically. In addition, Western blots were carried out with the same antibodies on choriocarcinoma cell lines. In placentae, a small number of villous and extravillous cytotrophoblast cells, as well as very few syncytiotrophoblast cells, stained intensively. Also, p53 was visualized in some nuclei of the placental basal plate, whereas stroma and endothelium were negative for p53. Jeg-3, JAR and BeWo also showed a positive nuclear reaction with all applied antibodies. In paraffin-embedded sections of human choriocarcinoma, staining was confined to the nuclei of malignant cells. The results suggest that p53 is overexpressed not only in malignant tumour cells but in certain trophoblast cell populations of the human placenta as well.
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PMID:Immunohistochemical evidence of p53 protein in human placenta and choriocarcinoma cell lines. 765 Jan 60

In the present study, we analysed human choriocarcinoma cell lines for abnormalities in the tumour-suppressor gene p53 by Southern blotting, Northern blotting, non-radioisotopic single-stranded conformational polymorphism (SSCP) and complementary DNA sequencing. In all cell lines (Bewo, GCH-1, GCH-2, SCH, JAR, JEG-3, NUC-1 and HCCM-5), no p53 gene abnormality was detected by using Southern blotting. p53 mRNA of the expected size was detected in all cell lines tested by Northern blotting. SSCP analysis revealed abnormalities of p53 cDNA in the SCH cell line. Sequencing analysis of the entire coding region of the p53 gene revealed that both alleles were expressed in the JEG-3 cell line, and one of the alleles contained a point mutation (G to T) in codon 167 (Gln to His). In the NUC-1 cell line both alleles were point mutated. One allele had a point mutation (A to T) that resulted in a codon 17 change (Glu to Asp), and another had a point mutation (A to T) that caused a codon 24 change (Lys to Asn). In the SCH cell line, AGG was inserted between codon 249 and 250; this insertion resulted in an abnormal structure of the p53 protein. In three out of eight human choriocarcinoma cell lines, a p53 gene abnormality was detected. Therefore our data demonstrate that p53 gene abnormalities are associated with choriocarcinoma cell lines.
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PMID:Analysis of the p53 gene in human choriocarcinoma cell lines. 781 56

Cell proliferative activity and the overaccumulation of P53 suppressor gene were evaluated in 26 cases of gestational trophoblastic disease and five cases with normal placentae. Formalin-fixed, paraffin-embedded histological sections were used for immunohistochemistry, utilizing the avidin-biotin-peroxidase technique and antibodies to PCNA (proliferative cell nuclear antigen) and to P53 (product of suppressor gene). Positive reactions for PCNA were graded from 1+ to 3+ (1(+)-less than 10% of cells; 2(+)-10-50%; 3(+)-more than 50%). Eight of 10 cases of choriocarcinoma (80%) showed moderate to strong reactivity for PCNA (2+ and 3+). All 9 cases with hydatidiform mole and 6 of 7 cases with partial mole also demonstrated 2+ and 3+ reactions for PCNA. There was minimal or no PCNA staining in the trophoblastic cells of normal placentae. Five of 10 cases with choriocarcinoma (50%) exhibited P53 overaccumulation as did 7 of 9 cases with hydatidiform mole (78%). In hydatidiform moles, P53 staining was limited to the areas of trophoblastic proliferation separate from chorionic villi. None of the partial moles or normal placentae showed P53 overaccumulation. It is concluded that the cell proliferative activity of choriocarcinomas as well as complete and partial hydatidiform moles are comparable. On the other hand, the mutation of P53 suppressor gene, as demonstrated by the overaccumulation of P53 protein, is seen only in true trophoblastic neoplasms, namely, choriocarcinomas and hydatidiform moles.
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PMID:Cell proliferative activity and mutation of P53 suppressor gene in human gestational trophoblastic disease. 790 85

In order to determine the p53 status of gestational trophoblastic neoplasia, 24 cases of molar pregnancies and two choriocarcinoma cell lines (JAR and JEG-3) were evaluated for the presence of mutations. The evaluation involved the whole coding sequence (i.e. exons 2-11) of the p53 gene with polymerase chain reaction (PCR) amplification of genomic DNA, followed by single strand conformation polymorphism (SSCP) and sequencing. Only one case of hydatidiform mole was found to have a missense point mutation (codon 295, CCT-->CTT, i.e. proline to leucine) of the p53 gene. The results suggest that p53 mutation is rarely involved in the pathogenesis of gestational trophoblastic neoplasia.
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PMID:Infrequent mutation in tumor suppressor gene p53 in gestational trophoblastic neoplasia. 795 57

The cellular mdm2 gene, which has potential transforming activity that can be activated by overexpression, is amplified in a significant percentage of human sarcomas and in other mammalian tumors. Proteins encoded by the mdm2 gene can bind to, and inhibit the function of, the protein product of the p53 tumor suppressor gene. As reported here, we have identified human choriocarcinoma cell lines that express high levels of mdm2 proteins as well as the p53 protein. Several lines of evidence demonstrate that the p53 in these tumor cells has a wild-type nucleotide sequence, although the protein exhibits an extended half-life. Further, the more than 100-fold overexpression of mdm2 proteins in these cells cannot be explained by gene amplification, elevated RNA expression, or altered protein stability; rather our data indicate that elevated mdm2 protein levels in these choriocarcinoma cell lines result from enhanced translation. This mechanism has not previously been implicated in the regulation of mdm2 gene expression, and it represents a novel means by which the potential transforming activity of the mdm2 oncogene could be activated.
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PMID:Enhanced translation: a novel mechanism of mdm2 oncogene overexpression identified in human tumor cells. 805 41

To examine the hypothesis that nutritional signals regulate trophoblast cell function, JEG-3 choriocarcinoma cells were treated with drugs that stimulate peroxisome proliferator-activated receptors (PPARs). These receptors are thought to mediate in part the effects of lipidic nutrients on gene expression. Because PPARs are modulated by interactions with retinoid-X receptors, we also examined the actions of the peroxisome proliferators in the presence of retinoids. Clofibric acid, a known peroxisome proliferator, suppressed JEG-3 cell growth in association with increases in the tumor suppressor p53 protein and its messenger RNA (mRNA). It reduced CG secretion and CG alpha and CG beta mRNAs in growing cells. However, clofibric acid did not induce peroxisome proliferation in the JEG-3 cells, as assessed by electron microscopy and immunostaining for catalase, a peroxisomal enzyme, or alter levels of mRNAs for peroxisomal proteins, sterol carrier protein-X/sterol carrier protein-2 and acyl-Coenzyme-A oxidase. The mitochondrial cholesterol side-chain cleavage enzyme, cytochrome P450scc, was modestly increased in some experiments. All-trans-retinoic acid and 9-cis-retinoic acid increased CG secretion and CG alpha and CG beta mRNAs, but clofibric acid blunted these stimulatory effects. WY 14,643, another peroxisome proliferator, also reduced CG gene expression without increasing mRNAs encoding peroxisomal proteins or altering P450scc mRNA. The mRNA for a human PPAR, NUC1, was demonstrated in JEG-3 cells, and NUC1 mRNA was shown to be upregulated by 8-bromo-cAMP. We conclude 1) that JEG-3 cells express a PPAR and are subject to regulation by PPAR stimulators; 2) that PPAR stimulation in JEG-3 cells does not promote peroxisome proliferation; and 3) that peroxisome proliferators and retinoids differentially regulate JEG-3 cell endocrine activities. We suggest from these findings that JEG-3 cells possess mechanisms to respond to nutrient cues.
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PMID:Peroxisome proliferators and retinoids affect JEG-3 choriocarcinoma cell function. 807 Mar 57

The p53 expression of normal trophoblasts (11 cases), partial moles (11 cases), complete moles (19 cases), and gestational choriocarcinoma (eight cases) were studied. We found that p53 is frequently expressed in gestational choriocarcinoma and in hydatidiform moles (mainly cytotrophoblasts), whereas syncytiotrophoblasts are generally spared. This finding supports the view that p53 expression is a reflection of proliferative capacity of cells rather than an indicator of neoplastic or malignant transformation. The greater p53 expression observed in complete moles as compared with partial moles is in keeping with the more pronounced trophoblastic hyperplasia and proliferative activity of complete moles. More interesting was the observation that p53 expression was also noted in normal trophoblasts, secretory endometrial glands, and decidual cells of the stroma. Therefore, it appears that the immunohistochemical expression of p53 can occur in a variety of situations, including neoplastic, proliferative, and nonproliferative conditions. Although p53 mutations are often the basis of excessive accumulation of mutant p53 protein in malignancies, other mechanisms may be involved in nonneoplastic conditions. These findings emphasize the need for caution in the interpretation of immunohistochemical expression of p53 protein.
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PMID:p53 expression in gestational trophoblastic disease. 860 23

This study investigates the extent of apoptosis in 53 testicular and ovarian germ cell tumors by using the in situ 3'-end DNA labeling technique on tumor sections. The tumors were also immunostained with antibodies to the p53 and bcl-2 proteins. The extent of apoptosis was highest in embryonal carcinoma (mean, 2.9%) followed by seminoma (mean, 1.1%), choriocarcinoma (mean, 0.7%) and immature teratoma (mean, 0.7%). In individual components of the mixed germ cell tumors the apoptotic index was in the same range as in the corresponding pure germ cell tumors. Mature teratomas rarely contained any apoptotic cells. Sixty-two percent of all the tumors expressed p53 protein. p53 expression was quantitatively strongest in embryonal carcinomas which also showed the highest level of apoptosis. Bcl-2 positivity could only be detected in some mesenchymal and epithelial components of the immature and mature teratomas; embryonal carcinomas, seminomas, or choriocarcinomas did not express bcl-2 at all. Our results show that the level of apoptosis in germ cell tumors associates with the histological type of the neoplastic component independent of whether it is singly present or a component of a mixed germ cell tumor. The results suggest that the quantity of p53 expression may contribute to the level of apoptosis in different tumor groups.
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PMID:Extent of apoptosis in relation to p53 and bcl-2 expression in germ cell tumors. 891 34

The mdm2 oncogene has transforming potential that is activated by overexpression. We previously reported the identification of human choriocarcinoma cell lines that have very high levels of mdm2 proteins as well as elevated levels of a stabilized wild-type p53 protein. Importantly, this mdm2 overexpression resulted from enhanced translation of mdm2 mRNA, a mechanism that had not previously been implicated in mdm2 expression control. The focus of this study was to investigate the breadth of enhanced translation of mdm2 mRNA in human cancers and to elucidate the basis for this translational activation. Here we present evidence that translational enhancement of mdm2 expression occurs in a variety of human tumor cells. Most of these samples also have high levels of wild-type p53 protein. However, there is no evidence for concomitant overexpression of the p53 target genes p21/waf1 and gadd45. Additionally, we demonstrate that the translational enhancement of mdm2 involves a preferential increase in mdm2 transcription that is initiated from the internal p53-responsive promoter region of this gene. The particular mdm2 transcripts that are generated contain a distinct 5' untranslated region and exhibit a significantly enhanced translational efficiency. These data provide a quantitative explanation for the overexpression of mdm2 proteins in this class of human tumors.
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PMID:Translational enhancement of mdm2 oncogene expression in human tumor cells containing a stabilized wild-type p53 protein. 927 29

The expression of the tumor suppressor/oncoprotein p53 has been investigated in normal human placental villous trophoblast, in vitro propagated invasive extravillous trophoblast, SV40 tumor antigen (Tag)-immortalized extravillous trophoblast, human cytomegalovirus (hCMV)-infected syncytiotrophoblast and malignant trophoblast (choriocarcinoma) cell lines (JAR, JEG-3 and BeWo) using quantitative enzyme-linked immunosorbent assay (ELISA) and Western immunoblot methods using monoclonal antibodies specific for wild-type and mutant p53. The normal villous and extravillous trophoblast cells expressed low levels of the wild-type p53 protein, whereas normal terminally differentiated multinucleated syncytiotrophoblast cells, as well as hCMV-infected syncytiotrophoblast, showed a higher expression of the wild-type p53 protein. SV40 Tag-immortalized invasive trophoblast cells also showed a high expression of the wild-type p53 protein which remained complexed with the Tag protein. All the choriocarcinoma cell lines over expressed the mutant form of the p53 protein. The increased expression of p53 protein in the SV40 Tag-immortalized invasive trophoblast and choriocarcinoma cells paralleled with increased expression of the mouse double minute 2 (mdm2) oncogenic protein. Transforming growth factor (TGF)-beta inhibited proliferation of normal extravillous trophoblast cells. The antiproliferative effects of TGF-beta were reduced in SV40 Tag-immortalized cells and non-detectable in choriocarcinoma cell lines JAR, BeWo and JEG-3. The inactivation of p53 owing to complexing with Tag in the immortalized premalignant trophoblast and p53 mutation in the malignant trophoblast may be responsible for their aberrant proliferation and refractoriness to antiproliferative effects of TGF-beta observed in these cells as compared to the normal trophoblast. These results may suggest the role of p53 protein in trophoblast differentiation, transformation and tumorigenesis.
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PMID:Altered expression of the tumor suppressor/oncoprotein p53 in SV40 Tag-transformed human placental trophoblast and malignant trophoblast cell lines. 936 7


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