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)

Using monoclonal antibodies, we have identified a series of tumor-associated antigens selectively expressed on tumor subtypes with distinct clinical behaviours. The mucinous antigen M344 and the gp200 surface antigen 19A211 are preferentially expressed on papillary superficial tumors and carcinoma in situ lesions of the bladder. The combination of these two antigenic markers in immunocytology and flow cytometry studies of exfoliated cells has improved the sensitivity of detection for bladder tumors. Moreover, the detection of M344- and 19A211-positive exfoliated cells from previously treated but currently tumor-free patients appears to be predictive of tumor recurrence on follow-up. These results, as well as results of bladder mapping studies in tumor patients, suggest that these antigenic changes occur in a premalignant stage and may provide tools to monitor the efficacy of chemopreventive measures. Other markers, such as the surface antigen T138 and the soluble molecules autocrine motility factor (AMF) and tumor collagenase stimulating factor (TCSF), are produced by primary or recurrent tumors with a higher metastatic potential. They may be useful in identifying high risk patients for distant failure. The highly restricted antigen 19A211 is also expressed on cervix condylomas and carcinoma. This observation led us to investigate a possible viral etiology of some bladder cancers. Using PCR techniques, we detected the presence of human papillomavirus (HPV) 16 DNA sequences in a significant proportion of bladder tumors. HPV positivity was inversely correlated with the presence of p53 mutations in exons 5-9 of the same tumors as measured by PCR-SSCP technique. This combination of markers may provide a basis for chemoprevention strategies targeted to distinct etiological events.
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PMID:Strategies of chemoprevention based on antigenic and molecular markers of early and premalignant lesions of the bladder. 130 95

To elucidate the role of p53 mutation in hepatocarcinogenesis in Taiwan, a hepatitis B viral infection hyperendemic area, exons 5 to 8 of the p53 gene in the tumor tissue of 61 hepatocellular carcinomas were amplified and sequenced. A total of 20 cases (32.8%) were found to have mutations; 36.6% (15 of 41) for the hepatitis B surface antigen positive group and 25.0% (5 of 20) for the hepatitis B surface antigen negative group. The corresponding normal liver showed no mutation. The mutation is widely distributed throughout exons 5 to 8. Only 4 cases (6.6%), all positive for hepatitis B surface antigen, had a specific hot spot mutation at codon 249 with G to T transversion. Our results show that scattered point mutations in p53 are not uncommon in hepatocellular carcinoma samples from Taiwan and may be important in the development of this cancer. However, the aflatoxin related specific mutation seems much less related to the genesis of hepatocellular carcinoma in Taiwan.
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PMID:Mutation of p53 gene in hepatocellular carcinoma in Taiwan. 132 23

The last decade has seen major advances in the acquisition of knowledge concerning both the cellular and molecular genetics of multiple myeloma. Although discrete and specific changes associated with the plasma cell disorders have yet to be identified, a pattern is emerging that one can associate with the plasma cell disorders. This pattern includes the frequent involvement of chromosomes 1 and 14, and in particular presence of the 14q+ abnormality. But in addition there are typically many other numeric and/or structural changes that can, in fact, involve almost any chromosome, but particularly chromosomes 3, 5, 6, and 7, as well as 11, 14, 17, and 18. The presence of one or more unidentified marker chromosomes is also a typical feature. The ongoing challenges include identification of a crucial initial genetic change (if such exists) as well as the factors contributing to the ongoing karyotypic evaluation that results in complex karyotypes in patients with advanced disease. There is no doubt that the complex karyotypic picture contributes to the major heterogeneity of plasma cells that occurs in malignant plasma cell disorders. Karyotypic complexity underlies heterogeneity in cell morphology, surface antigen expression, response to cytokines, and a variety of other functional characteristics. The aberrant expression of antigens normally found on other hematopoietic progenitors has led to speculation about the true nature of the stem cell in myeloma. The overriding challenge, however, is to fully understand the plasma cell disorders at the molecular level. Although changes have already been noted in the functions of C-myc, the ras family of oncogenes, Bcl-2 expression, and several so called anti-oncogenes such as p53, it is likely that we have only begun to scratch the surface in the area of molecular changes. The potential for involvement at multiple molecular sites and the possibility of complex interactions between gene segments is truly overwhelming. However, it is hoped that at the molecular level a pattern will ultimately emerge. It is most interesting, as previously discussed, that there is an interplay among C-myc, N-ras, Bcl-2, and the Epstein-Barr virus in the predilection for a plasma cell phenotype. Undoubtedly there is much more to learn, and it is truly exciting to finally have some tools and probes at hand to more effectively study the genome in multiple myeloma and related disorders.
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PMID:Cellular and molecular genetic features of myeloma and related disorders. 158 85

A new property, i.e. acquisition of insulin (insulin + dexamethasone)-mediated enhancement of anchorage independence by heterologous MuMTV-infected cells, is described. Hormone-mediated anchorage-independent growth enhancement in MuMTV-infected cells is followed by expression of a cell-surface antigen, recognized by allogeneic (C3H----AKR) anti-Thy 1.2 antigen serum. The absorption test and the use of monoclonal antibody to the Thy 1.2 antigen showed that hormone-dependent antigen on the cell surfaces of experimentally and naturally MTV-infected cells was different from the Thy 1.2 antigen itself. Utilization of anti-p53 ("protein of transformation") monoclonal antibody enabled us to identify this cell membrane antigen as p53.
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PMID:Hormone-dependent enhancement of neoplastic phenotype expression by MuMTV-infected heterologous cells, and MuMTV-induced cellular antigens. 632 29

To search for genes related to hepatocarcinogenesis, the differential display technique for eukaryotic mRNA was conducted. We have cloned a gene that encodes the CD24 protein from the cDNA library of human hepatocellular carcinoma (HCC). A single 2.1-kb mRNA was identified in HCC specimens and the HuH-7 HCC cell line but only rarely in small amounts in nontumor livers. In 79 unicentric HCC, CD24 mRNA was overexpressed in 52 cases (66%), found in trace amounts in 11, and not detectable in 16 (20%). In 12 cases of multicentric HCC, CD24 mRNA was overexpressed in 21 (68%) of 31 tumor nodules and was helpful for the determination of tumor clonal origin. There was an increased frequency of CD24 mRNA overexpression in patients younger than 50 years with HCC (86% versus 59%, P < 0.025), in serum hepatitis B surface antigen-positive individuals (74% versus 48%, P < 0.023), in those with an elevated serum alpha-fetoprotein level (82%, versus 56%, P < 0.04), and in HCC with alpha-fetoprotein mRNA expression (82% versus 56%, P < 0.04). There was a strong correlation of CD24 mRNA overexpression with p53 gene mutation in HCC (91% versus 46%, P < 0.0005) and poorly differentiated HCC (82% versus 53%, P < 0.0008). Despite its correlation with p53 mutation and the unfavorable outcome of HCC with p53 mutation, the CD24 mRNA expression did not correlate with tumor size, tumor invasiveness, or patient's prognosis. Thus, the CD24 gene expression appears to be a common event in HCC and may serve as an early but not prognostic biomarker for malignant transformation of hepatocytes.
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PMID:Cloning and expression of CD24 gene in human hepatocellular carcinoma: a potential early tumor marker gene correlates with p53 mutation and tumor differentiation. 755 54

Aflatoxin B1 (AFB1) has been postulated to be a hepatocarcinogen in humans, possibly by causing p53 mutations at codon 249. AFB1 is metabolized via the phase I and II detoxification pathways; hence, genetic variation at those loci may predict susceptibility to the effects of AFB1. To test this hypothesis, genetic variation in two AFB1 detoxification genes, epoxide hydrolase (EPHX) and glutathione S-transferase M1 (GSTM1), was contrasted with the presence of serum AFB1-albumin adducts, the presence of hepatocellular carcinoma (HCC), and with p53 codon 249 mutations. Mutant alleles at both loci were significantly overrepresented in individuals with serum AFB1-albumin adducts in a cross-sectional study. Mutant alleles of EPHX were significantly overrepresented in persons with HCC, also in a case-control study. The relationship of EPHX to HCC varied by hepatitis B surface antigen status and indicated that a synergistic effect may exist. p53 codon 249 mutations were observed only among HCC patients with one or both high-risk genotypes. These results indicate that individuals with mutant genotypes at EPHX and GSTM1 may be at greater risk of developing AFB1 adducts, p53 mutations, and HCC when exposed to AFB1. Hepatitis B carriers with the high-risk genotypes may be an even greater risk than carriers with low-risk genotypes. These findings support the existence of genetic susceptibility in humans to the environmental carcinogen AFB1 and indicate that there is a synergistic increase in risk of HCC with the combination of hepatitis B virus infection and susceptible genotype.
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PMID:Susceptibility to hepatocellular carcinoma is associated with genetic variation in the enzymatic detoxification of aflatoxin B1. 789 76

Bivariate flow cytometric analysis of p53 protein and DNA content was studied in archival specimens of hepatocellular carcinoma (HCC) from Chinese patients and corresponding benign liver tissues from a series of 51 patients at Sun Yat-sen University of Medical Sciences. Extracted nuclei were stained with the fluoresceinated monoclonal antibody PAb 1801, which recognizes human p53 protein (mutant and wild types). The nuclei were counterstained with the DNA stain propidium iodide. They were measured on an Ortho FC-200 flow cytometer and the data acquired and analyzed with an IBM 386 personal computer using Kusuda's Get Simple and List Simple software. Of the 51 hepatomas studied, 26 (51%) were p53 positive as compared with 4 (16%) of 24 samples of benign liver tissue from the same patients (P < .0257). The S-phase fraction of p53-positive HCC (12.3 +/- 8.8%) (SD) was significantly greater (P < .05) than for p53-negative HCC (7.4 +/- 7.2%). p53 Expression did not correlate with age, sex, alpha-fetoprotein, hepatitis B surface antigen, tumor size, tumor grade or survival rate. List Simple software permitted analysis of each specimen together with its isotype control (IgG1) on the same cytogram so that p53 expression could be determined separately for the diploid and aneuploid populations of aneuploid tumors and for tumor cells of diploid tumors in the various phases of the cell cycle. Since p53 (PAb 1801) expression can withstand formalin fixation and pepsin treatment of paraffin-embedded tissues, flow cytometric analysis of archival specimens is feasible, and clinical correlations such as these may be carried out in retrospective studies of other tumors.
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PMID:Bivariate flow cytometric analysis of p53 and DNA content in hepatocellular carcinoma. 804 59

Somatic mutation of the p53 oncogene/anti-oncogene allele has been shown to be involved in many different human solid tumors. Recently, there have been reports that p53 mutations are found to occur at high frequency (50%) in aflatoxin-related human primary hepatocellular carcinomas (HCC) (Hsu et al., 1991 Nature, vol 350, p. 427; Bressac et al., 1991 Nature, vol 350, p. 429). Most strikingly, a hotspot G to T mutation at amino acid position 249 was identified. These reports appear to contradict our earlier publications that although p53 mutation is found frequently in human HCC cell lines, it is rarely found in primary tumors. In this paper, we have further examined 20 different primary HCC samples (17 were hepatitis B surface antigen positive) and their adjacent nontumourous tissues, using restriction fragment length polymorphism (RFLP) analyses. Clear loss of heterozygosity (LOH) was found in only 3 out of 20 samples. All three samples were also found to carry a point mutation within the remaining p53 allele. None of these mutations was found to be at the proposed aflatoxin hotspot of amino acid 249. All three point mutations are of somatic origin. Ten samples, randomly chosen from the remaining 17 LOH negative HCC tumors, were analyzed further by DNA sequencing and Western blot analyses. No point mutations of p53 were found. Taken together with our previous report (Hosono et al., 1991, Oncogene vol 6, p. 237-243), we conclude that p53 mutation occurs infrequently, only approximately 18%, in HBV-positive primary hepatomas from Taiwan. Furthermore, p53 mutation appears to be acquired later in tumor development at least in some HCC samples.
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PMID:Infrequent mutation of p53 gene in hepatitis B virus positive primary hepatocellular carcinomas. 809 78

We studied 80 hepatocellular carcinomas from three continents for p53 gene (TP53) mutations and hepatitis B virus (HBV) sequences. p53 mutations were frequent in tumors from Mozambique but not in tumors from South Africa, China, and Germany. Independent of geographic origin, most tumors were positive for HBV sequences. X gene coding sequences of HBV were detected in 78% of tumors, whereas viral sequences in the surface antigen- and core antigen-encoding regions were present in less than 45% of tumors. These observations indicate that hepatocellular carcinomas are genetically heterogeneous. Mozambican-type of hepatocellular carcinomas are characterized by a high incidence of p53 mutations related to aflatoxins. In other tumors, the rarity of p53 mutations combined with the frequent presence of viral X gene coding sequences suggests a possible interference of HBV with the wild-type p53 function.
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PMID:Genetic heterogeneity of hepatocellular carcinoma. 829 Jun 6

A G:C-->T:A mutational hotspot at codon 249 of the p53 tumor suppressor gene has previously been identified in hepatocellular carcinoma (HCC) of patients from Qidong, China and southern Africa in which aflatoxin B1 (AFB1) and hepatitis B virus (HBV) are known synergistic risk factors. We have examined p53 mutation patterns of HCC from geographic areas in which the risk factors vary. Nine HCC lines and four hepatoblastoma lines (HB) were examined for p53 gene mutations and the relationship with HBV infection. Five of the nine HCC lines had homozygous mutation or deletion randomly distributed in exons 6-8, whereas none of the four HB cell lines had p53 mutations. One of the four HB lines (HepG2) had an N-ras mutation at codon 61 position 2. The p53 point mutations in the three HCC cell lines from Japan resulted in the amino acid changes of cysteine for tyrosine in cell line HuH 7 at codon 220 (A:T-->G:C), alanine for glycine in cell line HLF at codon 244 (G:C-->C:G), and serine for arginine in cell line HLE at codon 249 (G:C-->C:G). In addition, the deletion of 18 base pairs from codon 264 position 3 to codon 270 position 1 has resulted in the deletion of Leu-Gly-Arg-Asn-Ser-Phe from the amino acids sequences 256-270 in the Japanese cell line HuH 4. The cell line PLC/PRF/5 that showed p53 mutation at codon 249 (G:C-->T:A) with substitution of serine for arginine was derived from a South African patient. Our results indicate that whereas the p53 gene is not mutated in the HB cell lines, the HCC cell lines frequently contain an abnormal p53 gene. In addition, p53 point mutations were not detected in the four Japanese HCC cell lines that were positive for genomic integration of HBV X-gene and surface antigen gene. The three Japanese HCC cell lines with p53 mutations did not contain HBV sequences, indicating that hepatocarcinogenesis associated with p53 mutation does not require the genomic integration of HBV sequences.
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PMID:p53 gene mutation and integrated hepatitis B viral DNA sequences in human liver cancer cell lines. 838 56


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