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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We immortalized oral keratinocytes by transfecting them with recombinant human papillomavirus (HPV) type 18 DNA and established three cell lines. These lines were morphologically different from their normal counterpart, contained integrated entire HPV-18 DNA, and expressed the viral E6/E7 genes. The cells contained less p53 protein and more c-myc mRNA than normal cells. However, they proliferated only in keratinocyte growth medium (KGM) containing low calcium and were not tumorigenic in nude mice. To test the hypothesis that tumors result from the combined effect of a "high-risk" HPV and chemical carcinogens in the human oral cavity, we exposed the immortalized cells to the chemical carcinogen N-methyl-N'-nitro-N-nitrosoguanidine. Three chemically transformed cell colonies were isolated. These cells (a) proliferated well in both KGM and Dulbecco's modified minimum essential medium containing physiological levels of calcium; (b) were capable of proliferating in nude mice; (c) contained intact, integrated HPV-18 sequences; (d) transcribed substantially more HPV-18 E6/E7, transforming growth factor-alpha, and c-myc than the immortalized counterpart; and (e) contained, like the immortalized counterpart, less wild-type p53 protein and DCC message. These data indicate that human oral keratinocytes can be transformed by sequential exposure of normal keratinocytes to a "high-risk" HPV and chemical carcinogens.
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PMID:Combined effects of human papillomavirus-18 and N-methyl-N'-nitro-N-nitrosoguanidine on the transformation of normal human oral keratinocytes. 814 12

Medulloblastoma (MB) represents the most frequent malignant brain tumor of childhood but only a few cell lines and animal models of this primitive neuroectodermal tumor (PNET) have thus far been established. Using specific cell culture conditions, we were able to derive four human MB cell lines (MHH-MED-1-4) as well as a cell line from a spinal PNET (MHH-PNET-5). The four MB cell lines grew in suspension as floating cell aggregates or as slightly adherent cells. They consisted of undifferentiated cells that did not express markers of late neuronal or glial lineages such as neurofilaments or glial fibrillary acidic protein. They also lacked expression of major histocompatibility complex class I or II antigens on the cell surface. All four MB lines were positive for vimentin and neuron-specific enolase, whereas synaptophysin, neural cell adhesion molecule, galactocerebroside, GD2, GD3, and the A2B5 antigen were expressed inconsistently. In contrast, MHH-PNET-5 grew as adherent monolayer and expressed major histocompatibility complex class I antigen. By cytogenetic analysis, the lines were near diploid with clonal aberrations. The MB lines showed no losses of chromosome arm 17p by either cytogenetic or microsatellite analyses. The cell line MHH-MED-2 exhibited double minute chromosomes, amplification of the c-myc gene, and overexpression of c-myc mRNA and protein. N-myc, p53, and Rb protein expression were unaltered. All four continuously passaged MB cell lines and the MHH-PNET-5 line were xenotransplanted s.c. into athymic mice; three of four MB lines and the spinal PNET line gave rise to tumors. These cell lines will be useful tools for biological and preclinical studies on PNETs.
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PMID:Characterization of five new cell lines derived from human primitive neuroectodermal tumors of the central nervous system. 820 50

Two cultured cell lines derived from human squamous-cell carcinomas were established through xenografted tumors in nude mice by "Geneticin" treatment, which allows to eliminate contaminated mouse fibroblasts and obtain enriched tumor cells at the early stage of cultivation. Line KOSC-2 and KOSC-3 were each derived from a squamous-cell carcinoma of the oral floor and of the lower gingiva, respectively. Both lines grew in a cobblestone pattern, demonstrating their epithelial heritage. Giemsa-banding patterns by chromosome analysis confirmed that both lines are of human origin. Molecular analysis of cancer-related genes, including the Ha-ras, c-myc and p53 genes, was performed. KOSC-3 cells showed co-over-expression of p53 and c-myc mRNA, in addition to p53 point mutation at codon 248 with transition from CGG to TGG. However, loss of heterozygosity (LOH) on chromosome 17 was detected in both lines by Southern blotting. These cell lines provide a model for elucidating the mechanism involving p53 inactivation and c-myc-gene over-expression.
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PMID:Establishment of human oral-cancer cell lines (KOSC-2 and -3) carrying p53 and c-myc abnormalities by geneticin treatment. 831 15

The expression of the protein products and mRNA of c-fos, c-myc, p53, and c-raf was examined in normal renal tissues and biopsy specimens from 73 patients with various glomerular diseases. Immunofluorescent staining showed that there were cell nuclei stained for c-Fos, c-Myc, and p53, and cytoplasm positive for c-Raf, in the glomeruli of patients with proliferative types of glomerulonephritis, including IgA nephritis and lupus nephritis, and in patients with focal glomerular sclerosis. Glomerular expression of c-fos and c-myc mRNA was detected by in situ hybridization. The number of proto-oncogene-positive glomerular cells was significantly higher in lupus nephritis, IgA nephritis, and focal segmental sclerosis, as compared with minimal change nephrotic syndrome and normal specimens. In IgA nephritis, the population of glomerular cells positive for c-Fos and c-Myc and the grade of c-Raf immunoreactivity were significantly correlated with the proportion of proliferating cell nuclear antigen (PCNA)-positive glomerular cells, with histological grading of mesangial hypercellularity and matrix increase, and with the magnitude of proteinuria. These data indicate that proto-oncogene expression is associated with mesangial proliferation and matrix expansion in proliferative types of glomerulonephritis and in focal glomerular sclerosis.
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PMID:Proto-oncogene expression in human glomerular diseases. 877 42

To understand the role of the Src homology 2 (SH2) domain protein Shb in the signal transduction of tyrosine kinase receptor, NIH3T3 cells were transfected with a DNA construct expressing the Shb cDNA (NIHSHB cells). The NIHSHB cells expressed elevated levels of proteins with the estimated molecular weights of 77, 66 and 55 kDa as determined by immunoblotting. In contrast to the control cells, the NIHSHB cells failed to increase in cell number in the presence of 1% serum. This effect was largely due to apoptosis, since staining of pyknotic nuclei was observed using the terminal transferase labeling method. The NIHSHB cells displayed similar levels of c-myc mRNA and decreased contents of the p53 protein after culture in 1% serum compared with control cells. The addition of platelet-derived growth factor (PDGF-BB) restored the growth of the NIHSHB cells, whereas insulin-like growth factor-1 (IGF-1) failed to affect the proliferation of Shb overexpressing cells in 1% serum. We conclude that Shb overexpression is associated with cell degeneration under certain conditions, and that Shb could transduce apoptotic signals from tyrosine kinase receptors.
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PMID:Apoptosis of NIH3T3 cells overexpressing the Src homology 2 domain protein Shb. 880 85

Recent investigations have demonstrated p53 and Rb alterations in a subset of transitional cell carcinoma (TCC). Further genetic changes during tumor progression include overexpression of the c-myc gene in a significant number of mainly invasive bladder tumors. To study the possible interactions between these genes in TCC, urothelial cancer cell lines were chosen as an in vitro model. Expression and mutation of p53 was studied in 15 bladder cancer cell lines by immunocytochemistry, Western blot, polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing of double stranded PCR products of exons 4, 5, 7 and 8 of genomic DNA. C-myc expression and gene structure were studied using Northern and Southern blot techniques Rb protein expression was analyzed by Western blot. Twelve of 15 cell lines showed either p53 mutations or abnormal protein expression. Consistent with previous studies, five cell lines did not express Rb protein. None of the cell lines studied retained both tumor suppressor genes in a functional form. The c-myc gene appeared to be intact in all cell lines and copy numbers were close to normal. Northern analysis demonstrated that all cell lines expressed c-myc mRNA but evidence for altered regulation was found in at least two cell lines. Our data suggest that amplification or translocation are not the underlying mechanism for c-myc overexpression in urothelial tumors. No correlation between loss of Rb protein and c-myc expression was observed. The results presented here for the cell lines match well those obtained in vivo. Thus, these cell lines may provide a suitable model for further analysis of molecular alterations in urothelial cancer.
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PMID:Inactivation of tumor suppressor genes and deregulation of the c-myc gene in urothelial cancer cell lines. 883 85

Rat liver epithelial cells (RLE) are suspected to be pluripotent hepatic stem cells that give rise to a diverse variety of liver tumors. The molecular events responsible for transformation of these cells and the diversity of the tumor phenotypes remains to be fully elucidated. We examined the genotype and phenotype of RLE cells infected with retroviral shuttle vectors carrying a neomycin resistance (neor) Ha-ras or a lacZ gene. WBneoIII, WBrasIII and WBlacZ cell lines were examined for evidence of a transformed phenotype by comparing their behavior with the parental strain (WB-344) and with WBneo-C-II and WBrasII cells. Confluent cultures of WBneo-C-II and WBrasII cells were found to contain significantly higher numbers of total cells than the other cell lines. The growth rate of WBneo-C-II and WBrasII cells were faster than that of the parental cell line. Addition of epidermal growth factor (EGF) to the medium was found to stimulate the growth rate of WBneo-C-II cells and to induce anchorage independent growth (AIG). No cell line produced tumors in nude mice (nu/nu) except WBrasII cells. Radioimmunoprecipitation studies and sequencing of the p53 exons 5-8 indicate WBneo-C-II, and WBrasII cells produce a mutant p53. Northern blot analysis showed an increased expression of c-myc mRNA in WBneo-C-II and WBrasII cells. These results demonstrate that alterations in critical growth and differentiation controlling genes have occurred in WBrasII cells which may, independent of or in conjunction with ras insertion, cause the transformed phenotype.
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PMID:Phenotypic and genotypic analysis of rat liver epithelial cells infected with retroviral shuttle vectors. 891 62

A cell line designated CUMO-2 has been established from an undifferentiated ovarian carcinoma. The s.c. injection of cells into nude mice gave rise to fast-growing tumors, while the i.p. route induced a peritoneal carcinomatosis with ascites. Histopathologically, the transplanted s.c. tumors closely resembled the original tumor, but tumors developed in the peritoneal cavity were highly anaplastic. The epithelial nature of the cells was confirmed by ultrastructural analysis. Sequential cytogenetic analyses on early and late passages revealed highly aneuploid tumor cells with consistent structural aberrations of chromosomes 1, 3, 8 and 11. CUMO-2 cells were found to produce CA 125 in vitro and in vivo. Cytosol estrogen receptor (ER) was found but progesterone receptor (PR) was not measured. HLA typing indicated the presence of DR8 and DQw4. A gonadotropin-releasing hormone (Gn-RH) analog inhibited cell growth and Gn-RH receptor mRNA was detected by reverse transcription/polymerase chain reaction in this cell line. Administration of transforming growth factor beta 1 inhibited both cell growth and c-myc mRNA expression. This cell line demonstrated a conformational band shift in exon 7 of the p53 gene. It was a frameshift mutation.
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PMID:A new cell line from human undifferentiated carcinoma of the ovary: establishment and characterization. 903 Feb 46

Camptothecin, an antitumor drug that specifically targets topoisomerase I, induced IW32 erythroleukemia cells to differentiate along the erythroid pathway, as demonstrated by the increased mRNA and protein expression of hemoglobin. Unlike other chemically induced erythroleukemia cell differentiation, no c-myc mRNA down-regulation was observed in the early phases of drug treatment. Among the heme-synthesizing enzyme mRNAs that were analyzed, only that of the erythroid-specific delta-aminolevulinic acid synthase (ALAS-E) was stimulated. Vanadate or benzylphosphonic acid, which inhibited protein tyrosine phosphatases (PTPase), blocked the camptothecin-induced differentiation. Maximal inhibition was attained if vanadate was added within the first 6 hr of camptothecin treatment, after which vanadate gradually lost its effectiveness. Camptothecin-induced expression of beta-globin or ALAS-E transcript levels was inhibited in the presence of cycloheximide or vanadate. It was also shown that vanadate blocked differentiation of IW32 cells induced by sodium butyrate, VM-26, and p53. Increased PTPase activity could be observed 48 hr after cells were treated with camptothecin, VM-26, or sodium butyrate. Analysis of PTPase activity in the course of camptothecin treatment showed elevated levels of PTPase in the cytosol and the nucleus, with a greater increase demonstrated in the cytosol than in the nucleus. Our results suggest that by stimulating the beta-globin and ALAS-E gene expression, PTPase plays a critical role in the induced differentiation of IW32 erythroleukemia cells.
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PMID:Protein tyrosine phosphatase-dependent activation of beta-globin and delta-aminolevulinic acid synthase genes in the camptothecin-induced IW32 erythroleukemia cell differentiation. 910 19

C3H mouse embryo cells, which normally have low inherent spontaneous transformation, underwent malignant transformation while chronically infected with Mycoplasma fermentans or Mycoplasma penetrans. This mycoplasma-mediated oncogenic process had long latency (more than 7 weeks of persistent mycoplasmal infection) and showed multistage progression characterized by reversibility and irreversibility of malignant properties upon removal of M. fermentans from culture. Marked expression of H-ras and c-myc mRNA, but not N-myc, src, N-ras, or p53 mRNA, was found in the mycoplasma-transformed C3H cells that exhibited characteristic malignant properties of morphological changes and uncontrolled cell growth. However, at least up to the eleventh week of persistent mycoplasma infection, the marked expression of H-ras or c-myc mRNA in C3H cells depended on continued presence of the mycoplasma in culture. H-ras or c-myc mRNA rapidly declined to the undetectable low levels of nontransformed parental C3H cells, and all malignant properties of the once-fully-transformed C3H cells quickly reversed, if M. fermentans was eradicated from culture. In comparison, infection with M. penetrans for 7 or 11 weeks also induced a high level of H-ras, but not c-myc, mRNA expression in C3H cells. Despite having prominent amount of steady-state H-ras mRNA, these M. penetrans-infected C3H cells did not show any sign of malignant transformation. Thus, marked expression of H-ras gene alone was not sufficient to effect transformation in C3H cells. Interestingly, after a further prolonged (18 weeks) infection with either M. fermentans or M. penetrans, C3H cells revealed prominent chromosomal changes, expressed constitutively (with or without the presence of the transforming mycoplasmas) at high levels of both H-ras and c-myc mRNA and became permanently transformed. These cells were able to form tumors in animals.
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PMID:High-level expression of H-ras and c-myc oncogenes in mycoplasma-mediated malignant cell transformation. 911 27


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