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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Steady-state levels of myc, fos, p53, sis, and neu mRNAs were measured in eight variants derived from the Dunning R3327 rat prostate adenocarcinoma and compared to levels in normal dorsal prostate. Expression of the myb and erbB oncogenes in the Dunning tumors was below the limits of detection. Myc, p53, and sis mRNA levels in all tumors were at or above control levels. Fos mRNA levels were below control levels in four of five anaplastic tumors and were above control levels in the remaining tumors. A comparison of mRNA levels along the two Dunning lineages revealed that increased expression of these oncogenes did not correlate with tumor progression.
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PMID:Oncogene expression in prostate cancer: Dunning R3327 rat dorsal prostatic adenocarcinoma system. 321 75

The p53 gene is rearranged in an erythroleukemic cell line (DP15-2) transformed by Friend retrovirus. Here, we characterize the mutation and identify a deletion of approximately equal to 3.0 kilobases that removes exon 2 coding sequences. The gene is expressed in DP15-2 cells and results in synthesis of a 44,000-dalton protein that is missing the N-terminal amino acid residues of p53. The truncated protein is unusually stable and accumulates to high levels intracellularly. Moreover, it appears to have undergone a change in conformation as revealed by epitope mapping studies. This study represents the first description of an altered p53 gene product arising by mutation during neoplastic progression and identifies a region in the p53 protein molecule that plays a role in determining p53 stability in vivo.
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PMID:Deletion of 5'-coding sequences of the cellular p53 gene in mouse erythroleukemia: a novel mechanism of oncogene regulation. 354 84

The ability of p53 to activate or repress transcription suggests that its biological function as tumor suppressor is in part accomplished by regulating a number of genes including such required for inhibition of cell growth. We here give evidence that p53 also may regulate genes responsible for the proteolytic degradation of the extracellular matrix, which is considered a crucial feature for local invasion and metastasis of neoplastic cells. An important and highly regulated cascade of such proteolytic events involves the plasminogen activator system. We show that wild-type p53 represses transcription from the enhancer and promoter of the human urokinase-type (u-PA) and the tissue-type plasminogen activator (t-PA) gene through a non-DNA binding mechanism. Oncogenic mutants lost the repressing activity. In contrast, wild-type but not mutant p53 specifically binds to and activates the promoter of the plasminogen activator inhibitor type-1 (PAI-1) gene. Interestingly, one of the p53 mutants (273his) inhibited PAI-1 promoter activity. Our results suggest that altered function of oncogenic forms of p53 may lead to altered expression of the plasminogen activators and their inhibitor(s) and thus to altered activation of the plasminogen/plasmin system during tumor progression.
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PMID:Differential regulation of plasminogen activator and inhibitor gene transcription by the tumor suppressor p53. 747 1

p53 gene function and tumor cell proliferation are thought to be important parameters for tumor progression in bladder cancer. In this study immunohistochemistry and fluorescence in situ hybridization were used to determine the relationship between p53 alterations, tumor proliferation (Ki-67 Labeling Index), and numerical chromosomal aberrations in formalin fixed bladder tumors. p53 expression was associated with Ki-67 LI (p = 0.0014), polysomy 17 (p = 0.001) and polysomy 7 (p = 0.0241). This is further evidence for a significant role of the p53 gene in proliferation control and preservation of genomic stability.
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PMID:[Ki-67 fraction, p53 alteration and numerical chromosome aberrations (chromosomes 7 and 17) in formalin fixed bladder tumors]. 751 Dec 86

Neurofibromatosis type I (NFI) is a common autosomal dominant disorder with an increased risk for developing benign and malignant tumors. The NFI gene has been cloned and maps to 17q11.2, and the gene product acts as a tumor suppressor gene. Here we analyzed the role of mutations in TP53 in four malignant NFI tumors. Mutations were found in 3 out of 4 tumors. One of these mutations is a common missense mutation in codon 278 in one of the previously identified hot spots for mutations. The two other are hitherto unreported mutations, including a splice mutation of exon 3 and a nonsense mutation in exon 4. In addition, these four tumors also showed loss of heterozygosity (LOH) for markers on chromosome 17 in the region of TP53. Malignant NFI tumors are initiated by a somatic inactivation of the second NFI allele. Tumor progression, however, occurs by accumulation of additional genetic abnormalities, such as homozygous inactivation of TP53, as demonstrated in this paper.
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PMID:TP53 mutations are frequent in malignant NF1 tumors. 752 38

A variety of premalignant lesions, including Barrett's esophagus, colonic polyps, ulcerative colitis, primary sclerosing cholangitis, intraductal mucin secreting papillomatosis are now well recognized and accessible to direct endoscopic assessment and biopsy or brushing. This review emphasizes the potential usefulness of genetic markers, in particular Ki-ras oncogene and p53 tumor suppressor gene mutations, in the endoscopic surveillance of these premalignant conditions. The adjunction of Ki-ras and p53 assays in material collected during endoscopic procedures may help the clinician detect earlier and with a higher accuracy neoplastic progression.
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PMID:Use of genetic markers during endoscopic screening and follow-up of gastrointestinal precancerous lesions. 757 78

The t(11;14)(q13;q32) translocation, which juxtaposes the BCL1 oncogene with the Ig heavy chain locus, has been associated with an uncommon subtype of non-Hodgkin's lymphoma (NHL) termed mantle cell lymphoma (MCL). To date, no molecular marker that serves as an indicator of tumor progression or clinical prognosis has been described for NHLs with this translocation. We examined a panel of NHLs with t(11;14) for overexpression of p53 and correlated the results with single-strand conformation polymorphism (SSCP) analysis, karyotypic features, and clinical course. NHLs with t(11;14) were identified from 30 patients. The diagnosis was MCL for 23 of 30, small lymphocytic lymphoma for 4 of 30, and diffuse large-cell lymphoma for 3 of 30 cases. The results of immunohistochemistry analysis using a monoclonal anti-p53 antibody on paraffin-embedded specimens were compared with the SSCP data, the tumor karyotypes, and clinical course of each patient. DNA sequencing of exons was performed on cases that showed conformational changes by SSCP analysis. NHLs from 5 of 23 patients with MCL were positive for p53 overexpression. Deletions of chromosome 17p were identified in 2 of 30 cases, both of which were MCLs showing p53 overexpression. Two of the five MCLs with p53 overexpression showed evidence for TP53 mutations. None of the 18 MCLs negative for p53 overexpression showed conformational changes by SSCP. For these 18 patients with MCLs that did not overexpress p53, the median survival was 63 months, compared with 12 months for the 5 patients with MCLs positive for p53 overexpression (P < .001). These results suggest that p53 overexpression in MCL with t(11;14)(q13;q32) may serve as a marker of poor prognosis.
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PMID:p53 overexpression as a marker of poor prognosis in mantle cell lymphomas with t(11;14)(q13;q32). 757 80

Fifty-one randomly selected primary squamous cell carcinomas of the head and neck, derived from the larynx (n = 18) and pharynx (oropharynx, n = 18, and hypopharynx, n = 15) were analyzed with centromeric probes for chromosomes 1, 7, 9, 11, 17, and 18 to study numerical aberrations, chromosome imbalances, and aneuploidy by fluorescence in situ hybridization. The tumors were grouped into nonmetastasizing (N0) tumors (from patients clinically free of lymph node metastases for at least 18 months after surgery, n = 25) and metastasizing (N1-3) tumors (n = 26). We found a significant association between the tumor ploidy and the nodal status; in the N0 group, diploidy prevailed, and the most common aberration was loss to monosomy for chromosome 9 (44%), whereas in the N1-3 group, aneuploidy predominated (P = 0.002). Specifically, these genomic changes associated with progression to metastasis were: (a) tetrasomic or polysomic chromosomes were detected in 17 of 26 N1-3 tumors but in none of the 25 N0 tumors (P < 0.0001); (b) heterogeneous chromosomal copy numbers (i.e., extensive chromosomal imbalances) were also much more frequent in the N1-3 tumors (69.2% versus 24.0% in the N0 group; P = 0.018); and (c) loss of chromosome 9 (73%) and gains of chromosomes 7 (35%) and 17 (31%) persisted, but in addition, loss of chromosome 18 occurred in 31%. Overexpression of the p53 protein correlated with an increased incidence of chromosomal imbalances and aneuploidy (P < 0.001) and, hence, constituted an additional risk factor. The lower metastatic potential of larynx tumors as compared with tumors from the pharynx was reflected by a lower incidence of these genomic changes. These specific patterns of chromosomal aberrations can characterize and distinguish different stages of tumor progression of squamous cell carcinomas of the head and neck and should be valuable diagnostic and prognostic markers.
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PMID:Distinct nonrandom patterns of chromosomal aberrations in the progression of squamous cell carcinomas of the head and neck. 758 47

Dietary folate/methyl deficiency provides a unique model of endogenous hepatocarcinogenesis in which to study progressive alterations in DNA methylation patterns during tumor progression in vivo. Weanling male F344 rats were given a semi-purified diet deficient in the methyl donors choline, methionine and folic acid for a period of 9 weeks. Using a genomic sequencing procedure based on the PCR amplification of bisulfite-modified DNA, the methylation status of individual CpG sites within exons 6 and 7 of the p53 gene in liver samples from control and deficient rats was determined. Treatment of denatured nuclear DNA with sodium bisulfite quantitatively converts all cytosine residues to uracil which are then amplified as thymine in the PCR reaction. In contrast, 5-methylcytosine is resistant to bisulfite deamination under the reaction conditions and is amplified as cytosine. Automated sequencing of bisulfite-modified DNA will then elucidate the methylation status of each cytosine residue within a defined gene sequence. In addition to evaluation of the methylation status of the p53 gene, the relative activity of the DNA methyltransferase was also quantified in nuclear extracts from control and folate/methyl deficient rats. The results indicate that specific 5-methyl cytosines within the hepatic p53 gene from methyl deficient rats are resistant to demethylation despite the diet-induced decrease in S-adenosylmethionine and the increase in cell proliferation associated with this dietary intervention. Progressive demethylation was observed at other methylated cytosine residues in folate/methyl deficient rats after 9 weeks despite a paradoxical increase in DNA methyltransferase activity. The application of this sequence-specific technology will allow the definition of the methylation status of every CpG site within a coding sequence or promoter region and should provide new insights into mechanisms and consequences of methylation dysregulation during progressive multistage carcinogenesis.
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PMID:Differential sensitivity to loss of cytosine methyl groups within the hepatic p53 gene of folate/methyl deficient rats. 758 11

In the present study we investigated the pathogenetic role of c-myc, bcl-2, and lyt-10 oncogenes, bcl-1 locus, and p53 suppressor gene in a representative panel of cutaneous lymphomas, including 25 cases of cutaneous B cell lymphoma (CBCL) and 29 cases of cutaneous T cell lymphoma (CTCL). In our analysis four cases of CBCL were found rearranged for bcl-2 and two for the bcl-1 locus. Two cases of CTCL and one case of CBCL were found rearranged for lyt-10. No rearrangements of c-myc oncogene were found in CBCL. Analysis of p53 gene showed mutation only in one case of mycosis fungoides in tumoral stage, at codon 163 of p53 gene (TAC-->CAC; Tyr--> Asp). Our data suggest that in primary CBCL bcl-2 oncogenes and bcl-1 locus are rarely involved. Furthermore, in primary CTCL p53 gene is not affected at significant frequency. The occurrence of p53 mutation in a patient affected by mycosis fungoides in tumoral stage may represent an involvement of p53 gene in tumor progression of CTCL, a finding observed in several types of human cancer.
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PMID:bcl-1, bcl-2, p53, c-myc, and lyt-10 analysis in cutaneous lymphomas. 759 96


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