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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

P44 Ro (Mel) is a human malignant melanoma cell line derived from a testicular metastasis in a DNA repair deficient, xeroderma pigmentosum patient. This line harbors a N-ras gene mutated in codon 61. To investigate other cellular genes possibly contributing to the expression of its transformed phenotype, four XP44 revertant cell lines were isolated by different selection procedures and the association of the level of expression of various oncogenes (including N-ras) and tumor suppressor genes with the selection for the revertant phenotype was determined. The revertants exhibited a significant but variable degree of phenotypic reversion, according to the selective pressure to which they were submitted, and a phenotypic stability dependent on their constant maintenance in selective medium. Back-revertant lines were isolated by culturing revertant lines in control medium for several weeks. The comparison between parental, revertant and back-revertant cells has revealed that, beyond the mutation in codon 61 of N-ras, two groups of genes appear to be also implicated in the transformation process of XP44 RO (Mel) cells: one group, comprising pim A, trk, Rb and p53, whose expression is independent of the cell selection conditions; the other group, comprising Ha-ras, N-ras, neu 1, fos and met H, whose expression is more or less dependent upon such conditions. The myc gene is apparently not involved in this phenomenon. These results, besides strengthening the concept that carcinogenesis is a multigenic process, suggest that diverse mechanisms can lead to the transformed phenotype, but that these mechanisms might have some pathway(s) in common.
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PMID:Cellular genes possibly involved in the transformation process of the human melanoma cell line XP44 RO (Mel). 765

In vitro exposure of tumorigenic cell lines to the chemotherapeutic agent PALA (N-(phosphonoacetyl)-L-aspartate) usually results in cell death (shown here to be apoptosis), followed by clonal growth of rare survivors. On the other hand, normal diploid cells respond to PALA by arresting in G1 and G2 of the cell cycle. It was previously suggested that growth control mechanisms might exist to prevent cells from entering S phase under toxic conditions and that genes involved in such mechanisms were mutated or deleted in tumor cells. Interestingly, the tumor suppressor gene p53, a putative G1 control gene, was shown to mediate PALA-induced growth arrest. However, growth arrest occurs in cells that lack wild-type p53, suggesting that other genes are involved as well. To identify these genes, we have generated whole cell hybrids between mouse melanoma and normal human fibroblast cells. At early passage, a whole cell hybrid (BHF12) responds to PALA with growth arrest, while at later passage, the same hybrid undergoes apoptosis. To determine which human chromosomes are required for the PALA-induced growth arrest phenotype, we isolated subclones of the hybrid and tested them for their PALA response. FISH (fluorescence in situ hybridization) and PCR (polymerase chain reaction) amplification have been used to identify the human chromosome content of BHF12 and its subclones. Several human chromosomes, in addition to chromosome 17 (the location of p53), are consistently associated with the growth arrest phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification of chromosomes implicated in suppression of apoptosis in somatic cell hybrids. 765 40

In the present study, we investigated the expression of the tumour suppressor protein p53 in 113 primary and 43 metastatic malignant melanomas by immunohistochemistry, and correlated the findings with clinicopathological parameters such as histological melanoma subtype, thickness of primary melanomas (Breslow thickness) and patient outcome. In primary melanomas, the polyclonal anti-p53 antibody CM-1 detected immunoreactivity in 70% of the lesions, predominantly in the cytoplasm. Signals were observed in this cellular compartment in 57% of the melanomas, whereas in 32% nuclear p53 over-expression was detected. Immunohistochemistry, using the monoclonal antibody DO-1, revealed lower staining frequencies. However, both antibodies showed congruent results in approximately 80% of the cases. Overall, immunoreactivity was observed in 73% of superficial spreading melanomas, but only in 52% of lentigo maligna melanomas. This difference (P < 0.001) was mainly due to a lower frequency of cytoplasmic immunoreactivity (P < 0.002). There was no difference with respect to cytoplasmic and nuclear immunoreactivity between thin (< 1 mm thickness) and thicker primary melanomas. Staining frequencies detected in metastatic lesions seemed to be lower than in primary tumours. In 103 primary melanomas, follow-up data for at least 5 years were available. In 71% (54 of 76) of the primary melanomas which did not recur, and in 78% (21 of 27) of tumours with subsequent metastases, p53 over-expression was detected by CM-1. However, this difference was not statistically significant. The results of the present study indicate that immunoreactivity to anti-p53 antibodies is a common observation in malignant melanomas, with staining signals predominantly found in the cytoplasm of cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of p53 protein in malignant melanoma: clinicopathological and prognostic implications. 766 36

We have examined melanocytic cells derived directly from fresh biopsy tissue for the presence of p53 mutations. Using selective media that permits growth of melanocytes and inhibits growth of fibroblasts and keratinocytes, we established short-term, primary cultures of melanocytes from skin biopsies of common acquired nevi, dysplastic nevi, and from metastatic melanoma. Using PCR-single-stranded conformational polymorphism analysis, we have detected p53 mutations in 2 of 11 benign compound nevi and 2 of 5 dysplastic nevi. All nevi positive for p53 mutations were derived from patients who previously had cutaneous moles and three of the four had a family and/or personal history of melanoma.
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PMID:Detection of p53 mutations in benign and dysplastic nevi. 767 Dec 35

Alterations in the function of p53, a tumor suppressor gene, have been postulated as a principal underlying mechanism involved in the loss of cell cycle control in human malignancies. Because p53 dysfunction is generally associated with protein overexpression, immunocytochemistry is a valuable technique for the analysis of p53's functional status. We tested the hypothesis that loss of p53 function is a critical event in the early development and progression of human malignant melanoma and can lead to alterations in cell proliferation. We performed an immunocytochemical study in archival fixed, embedded specimens that included 102 melanocytic lesions ranging from benign nevi to metastatic melanoma. In addition to p53, we assessed the p53-associated protein, mdm-2, and markers of cell cycle status (the MIB-1-defined cell proliferation marker; proliferating cell nuclear antigen; and statin, a 57-kDa nuclear protein expressed preferentially by G0 cells). Tumor expression of all nuclear proteins was scored in a semiquantitative fashion related to the fraction of positive tumor nuclei. The overall incidence of significant p53 overexpression was low (8% of primary and 14% of metastatic melanomas). Analysis demonstrated strong correlation between increasing p53 expression in primary versus metastatic lesions (chi 2 analysis, P = 0.001). Correlation was found between increased MIB-1-defined cell proliferation and p53 overexpression in primary melanomas (P = 0.02). Detectable mdm-2 expression was significantly correlated with p53 overexpression (P = 0.02). Comparison of statin and proliferating cell nuclear antigen indices demonstrated inverse correlation (chi 2 , P = 0.03) in the combined groups, but within the metastatic group there was a subset of cases strongly expressing the two markers.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:p53 and mdm-2 expression in malignant melanoma: an immunocytochemical study of expression of p53, mdm-2, and markers of cell proliferation in primary versus metastatic tumors. 767 73

Forty-six cases of sporadic melanoma have been investigated for loss of heterozygosity at 4 loci: D11S29 (11q23), YNZ22 (17p13.3), TP53 (17p13.1); and NM23 (17q22). Each of the loci is thought to be important in the pathogenesis of other tumours. Mutations were found infrequently at the YNZ22, NM23, and TP53 loci. At D11S29, however, the frequency of mutation in the melanoma samples was high (67%) and mutations at this locus were associated with younger age at presentation. This region of chromosome 11 is also commonly mutated in breast cancers and haematological malignancies. Genetic aberrations at D11S29 may therefore represent nonspecific mutations found in several malignancies or part of a pathway common to the malignant phenotype.
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PMID:Loss of heterozygosity in malignant melanoma at loci on chromosome 11 and 17 implicated in the pathogenesis of other cancers. 768 71

Suppressor oncogene p53 is expressed more frequently in the nodular portion than the superficial spreading portion of the same melanoma. PCNA expression follows the same pattern but it is strongly expressed already in the superficial spreading portion. CD34 is found to label dermatofibrosarcoma protuberans. There is the mixture of negative strands but the immunostains are predominantly positive in the three cases studied. Neurogenic tumors are reactive but the intensity of staining is only moderate. Fibrous histiocytoma, dermatofibroma and other fibrohistiocytic tumors are non-reactive. CD34 is expressed in the outer root sheath of hair follicle below the sebaceous gland level. A case of piloepidermal cyst is CD34 positive. CD34 is expressed in vascular endothelial cells; not only hemangiomas but also lymphangiosarcoma is CD34 positive. A case of indeterminate cell histiocytosis following scabies and superficial variant of clear cell sarcoma are discussed as examples of new entities.
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PMID:Current topics of immunohistochemistry as applied to skin tumors. 769 83

According to the current concept of carcinogenesis, the alterations of p53 tumor suppressor gene have been the most frequently detected in both human cancer cell lines and cancer tissues freshly isolated. This study was conducted to investigate the p53 gene alteration in malignant melanoma. Nineteen tumor tissues were obtained from 19 patients with malignant melanoma and examined for the expression of p53 protein by immunohistochemical staining with mouse monoclonal anti-p53 antibody, NCL-p53-DO-7. Twelve out of 19 cases (63%) showed positive reactions for p53 protein: 26, 21 and 16% of which had low, intermediate and high reactivity, respectively. p53 alteration more frequently expressed in female (10/12) than male patients (2/7) with malignant melanoma (p < 0.05). The incidence of expression of p53 protein was compared according to the stages and the sites of tissue obtained. The positive rate for p53 protein was not significantly different between the stages. The positive rates for p53 protein were five out of five (100%), one out of two (50%) and six out of twelve (50%) in tissues obtained from the metastatic, lymph node, and primary sites, respectively. The difference in the positive rates, however, is not statistically significant. These results suggest that p53 gene is a frequent target for mutation in the development of malignant melanoma.
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PMID:Aberrant expression of p53 gene product in malignant melanoma. 770 85

The 9p21 region of human chromosome 9 is a hot spot for chromosomal aberrations in both cultured cell lines and primary tumors. This region contains a gene, P16 (also called MTS1, CDKN2 and p16INK4), that encodes a presumptive negative cell cycle regulator called p16. P16 is deleted or mutated at high frequency in a variety of tumor cell lines including melanoma and bladder carcinoma lines. As such, it is likely to be a tumor suppressor gene. Here we show that P16 is mutated in primary bladder carcinomas (3 of 33) and melanomas (5 of 34). These findings support studies that show P16 mutations are not solely a product of growth in tissue culture but rather are involved in formation of tumors in viva. Some bladder primary tumors and some bladder and melanoma tumor cell lines contain mutations in both P16 and P53 at frequencies that suggest that p53 and p16 function in different pathways, each of which is important in suppressing malignant transformation.
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PMID:Genetic evidence in melanoma and bladder cancers that p16 and p53 function in separate pathways of tumor suppression. 774 14

The combination of recombinant human fibroblast interferon (IFN-beta) and the antileukemic compound mezerein (MEZ) induces terminal differentiation with an irreversible loss of proliferative capacity in human melanoma cells. Using subtraction hybridization, cDNAs were identified that display enhanced expression in terminally differentiated and growth arrested human melanoma cells (Jiang and Fisher, 1993; Jiang et al., 1994a). A specific melanoma differentiation-associated (mda) cDNA, mda-6, is described whose expression inversely correlates with melanoma progression and growth. mda-6 is identical to WAF1/CIP1/SDI1 that encodes the M(r) 21,000 protein (p21) that is an inhibitor of cyclin-dependent kinases. Actively growing normal melanocyte, SV40-immortalized human melanocyte and dysplastic nevus cell lines synthesize elevated levels of mda-6 mRNA; whereas, actively proliferating radial and early vertical growth phase primary melanomas as well as metastatic human melanoma cells produce reduced levels of mda-6 mRNA. Treatment of primary and metastatic human melanoma cells with IFN-beta + MEZ results in growth inhibition and an increase in mda-6 expression. mda-6 expression also increases when human melanoma cells are grown to high saturation densities or when grown in serum-free medium. Using anti-p53 and anti-p21 antibodies, an inverse correlation is found between p53 and p21 protein levels during growth arrest and differentiation. Induction of growth arrest and terminal differentiation in H0-1 human melanoma cells by IFN-beta + MEZ results in a temporal decrease in wild-type p53 protein levels with a corresponding increase in p21 levels. In the Matrigel-assisted melanoma progression model, mda-6 expression decreases in early vertical growth phase primary human melanoma cells selected for autonomous or enhanced tumor formation in nude mice. In metastatic human melanoma cells displaying a loss of metastatic potential resulting from introduction of a normal human chromosome 6, mda-6 mRNA levels increase. Taken together, these studies indicate that mda-6 (p21) may function as a negative regulator of melanoma growth, progression and metastasis.
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PMID:The melanoma differentiation-associated gene mda-6, which encodes the cyclin-dependent kinase inhibitor p21, is differentially expressed during growth, differentiation and progression in human melanoma cells. 775 61


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