Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

p53 expression is strongly modulated during the process of induced differentiation, at the same time as both cell cycle and genetic expression become modulated, giving rise to a commitment to terminal differentiation. We took advantage of two murine cell lines inducible for differentiation, an erythroleukemia and a melanoma cell line, to outline common features of the regulation of p53 expression during the differentiation process. We found that p53 mRNA decreased early after induced differentiation and that regulation was controlled at a posttranscriptional level. Our data showed that this regulation affects p53 pre-mRNA maturation. Because, in both systems used, actinomycin D treatment abolished the inducer-mediated decrease of p53 mRNA, we looked for induced RNAs potentially involved in this process. Using different parts of the p53 gene and flanking regions as probes, we identified three RNA species whose expression is modulated during induced differentiation. A first species is made of high molecular weight RNAs that accumulate in the nuclear compartment and seem to represent antisense transcripts of the p53 gene. A second species, 1.3-kb long, was found to accumulate in the nucleus of induced MEL cells and was homologous to a restricted part of the first intron of the p53 gene due to the presence of a B1 repetitive element in an antisense orientation with respect to the p53 pre-messenger RNA. Finally, a family of B2-containing RNAs was observed in both cytoplasmic and nuclear compartments. The variation in the amounts of sense and antisense RNAs, respectively, suggested an interesting speculative model for the maturation of B2-containing pre-messenger RNAs.
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PMID:Antisense RNA and p53 regulation in induced murine cell differentiation. 134 Jan 59

Using CM-1 antibody directed against the human p53 protein, high levels of mutant p53 protein expression were found in 12 out of 18 malignant choroidal melanomas. In contrast, we failed to observe elevated p53 expression, indicating the absence of p53 mutation in seven choroidal naevi, a potentially premalignant condition that can progress to form malignant melanoma. For two choroidal melanomas, we demonstrated that high levels of p53 protein were accompanied by exon 7 mutations. The mutations were found at codon 238, TGT-->TTT and codon 253, ACC-->AGC. These observations suggest that acquisition of abnormalities of the p53 gene may be an important step in the development of malignant melanoma.
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PMID:Increased expression and mutation of p53 in choroidal melanoma. 141 33

We have developed new methodology for quantifying antibodies to the p53 tumor suppressor gene product in human serum. The assay involves solid-phase immobilization of a monoclonal anti-p53-specific antibody that is then reacted with a tumor cell line lysate containing mutant p53. The immunopurified p53 antigen acts as an immunosorbent for the serum p53 antibodies that are then detected by reaction with a goat anti-human immunoglobulin G antibody labeled with alkaline phosphatase (ALP). ALP activity is then measured with enzymatically amplified time-resolved fluorometry. The developed assay has many advantages over the radioactively labeled techniques previously used. In a preliminary clinical study involving 790 patient sera, we have identified 16 positive samples (2%). Highest titers were observed in a patient with melanoma and two breast cancer patients. Further studies are needed to improve the sensitivity of this test and to evaluate its possible use for cancer diagnosis, prognosis or monitoring of therapy.
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PMID:Antibodies to the p53 tumor suppressor gene product quantified in cancer patient serum with a time-resolved immunofluorometric technique. 147 69

The purpose of the present study was to examine the expression of p53 protein in malignant melanomas of the nodular sub-type, with special reference to the role of p53 alterations in the development of metastases. Increased expression of p53 protein was found in 29 of 30 cases using PAb1801 monoclonal antibody (MAb) and flow-cytometric detection on archival material. A large proportion of the cells were positive in a majority of the cases. The level of expression was not correlated to DNA ploidy or to subsequent development of local metastases. However, a significant decrease in p53 protein expression was observed in metastatic lesions, as compared with the corresponding primary tumors. Our results indicate that p53 alterations may be an early event in melanoma development, since almost all cases were affected, and that metastatic spread appears to be parallelled by decreased p53 protein expression.
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PMID:Expression of p53 protein in cutaneous melanoma. 150 Feb 18

The molecular genetics of melanoma is little understood and has concentrated largely on DNA analyses. We have examined mRNA levels of 21 different oncogenes, antioncogenes, growth factors and proteases in cultured melanocytes and 17 melanoma cell lines. C-mel, c-erb-B2, c-myc, c-src-1, p53, platelet derived growth factor A chain, gro, transforming growth factor alpha, epidermal growth factor receptor and tissue plasminogen activator were all expressed in at least some cell lines. Most striking was the finding that there are significant intercorrelations of c-myc, p53 and c-src-1 levels, and between p53 and c-erb-B2, which may be due to common regulatory control of these genes in cells of the melanocytic lineage.
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PMID:Gene expression in melanoma cell lines and cultured melanocytes: correlation between levels of c-src-1, c-myc and p53. 169 9

In animal systems, complete and permanent eradication of tumours can be achieved by adoptive transfer of MHC-restricted T cells, combined with IL2. In certain types of human cancer (melanoma and perhaps renal cell carcinoma), tumour-specific T cells are probably the therapeutically most active cells among LAK or TIL cells. To prove these points, it is necessary to conduct trials with cloned tumour-specific T cells. Other potentially immunogenic tumors are cervical carcinoma, associated with human papilloma virus, and Burkitt's lymphoma, associated with Epstein-Barr virus. Most other human tumours, caused by subtle mutations in proto-oncogenes, are likely to be poorly or non-immunogenic. It is worthwhile trying to overcome this by vaccination with IL2 or IFN gamma-producing tumour cells or by deliberate vaccination with desirable targets for tumour-specific CTL such as the products of point-mutated oncogenes, including ras (Jung and Schleusener, 1991) and p53 (Rodriguez et al., 1990; Halevy et al., 1990), provided the relevant peptides are processed and bound to MHC class I molecules. Other potential targets are breakpoint peptides of translocated oncogene products such as bcr/abl (Van Denderen et al., 1990). In viral systems, it has already been established that peptide vaccination for protective CTL induction is feasible (Aichele et al., 1989; Schulz et al., 1991; Kast et al., 1991).
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PMID:T-cell immunotherapy of cancer. 175 15

Immunogenic tumor antigens have been sought through a variety of paradigms for several past decades. Recent developments in antigen presentation have radically changed the prism through which we view these enigmatic antigens. This article discusses the small but growing treasure chest of these antigens--stress-induced proteins, the P1AB antigen of the P815 mastocytoma, the p53 tumor suppressor protein, the gp95/p97 antigen of human melanoma, mucins and others.
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PMID:Protein tumor antigens. 175 84

It has been well established that sometimes cancer clusters within specific families. This has suggested the possibility that some of those families might carry genetic defects which provide susceptibility to specific cancers. Retinoblastoma, an embryonal tumor of the eye represents an extreme example of a tumor which has a dramatic genetic component. Several studies have shown that inactivation at the retinoblastoma gene is probably both necessary and sufficient to initiate retinoblastoma formation. Patients who survive the inherited form of the disease are at risk of developing mesenchymal tumors, melanoma and brain tumors in as high as 10% of the patients before they are 40 years old. Because the product of the retinoblastoma gene, p105Rb, is expressed in all cell types, the obvious question is what accounts for these tissue specific differences in the role of p105Rb. Small cell lung carcinomas virtually all have associated mutations in the Rb gene and yet those tumors do not occur at a significantly increased frequency in patients with the hereditary form of retinoblastoma. In order to identify genes which might predispose to some of the more common adult malignancies, we have focused on one form of hereditary breast cancer. We chose a rare form of hereditary breast cancer which occurs in families with sarcomas (Li-Fraumeni Syndrome). By use of the candidate gene approach we tested which germ line p53 mutations were found in affected family members with Li-Fraumeni Syndrome (LFS). We have found that virtually all of the families with LFS have germ line p53 mutations, and that these tumors have undergone inactivation of the remaining wild-type p53 allele. In order to investigate the role of germ line p53 mutations outside of these rare families, we have begun to investigate other high risk groups. These results indicate that de novo germ line p53 mutations certainly occur in these high risk groups. These findings along with the recognition of the germ line p53 mutations in families with LFS provide clues about the importance of uncovering hidden susceptibilities from germ line tumor suppressor genes not only for the care of patients, but also for understanding the primary events that normally regulate the growth of cells in various tissue.
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PMID:Cancer risks from germ line tumor suppressor gene mutations. 184 52

Nine metastatic melanoma cell lines and two melanocyte cell lines were analyzed for point mutations in highly conserved regions of the p53 gene. No mutations were detected in the two melanocytic cell lines and in eight melanoma cell lines. However, a C----T transition at codon 248, resulting in a substitution of tryptophan for arginine, was found in one melanoma cell line. On immunohistochemical staining, only this cell line showed reactivity for mouse monoclonal antibody 1801, which is immunoreactive with human p53 protein. The original paraffin-embedded specimen from which this mutant cell line was established was obtained, and sequence analysis detected the identical mutation in the p53 gene as that seen in the derived cell line. This is the first report indicating point mutations in the p53 gene in malignant melanocytic tissues.
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PMID:Mutational analysis of the human p53 gene in malignant melanoma. 192 72

Mutant p53 has been noted in a variety of human malignancies including carcinomas of lung, breast, and colon, which have also been reported to have frequent karyotype anomalies involving the locus of the p53 gene (17p13). Whereas chromosomal abnormalities of chromosomes 1, 6, and 7 have been noted previously in melanoma, frequent aberrations in chromosome 17 have not been reported previously. Due to the common mutation of this locus in so many types of neoplasms, a range of melanomas from different stages of tumor progression were examined immunohistochemically for expression of mutant p53, in order to assess its prevalence and consider the role of this oncogene in the biological progression of melanoma. Forty-five of 53 (85%) specimens from a range of primary and metastatic melanomas were found to have detectable evidence of p53 gene mutation, by virtue of the immunohistochemical detection of mutant p53 protein. Significantly increased prevalence of mutant p53 was found in metastatic melanoma, compared with primary tumors (P less than 0.05). These findings represent one of the highest incidences of this oncogenic mutation yet recorded in a human malignancy and support the concept that p53 may have a functional role in development of the metastatic tumor phenotype.
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PMID:Expression of mutant p53 in melanoma. 193 61


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