Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently p73, a novel p53 homologous tumour suppressor gene, has been cloned and mapped to chromosome 1p36. Like p53, important functions of p73 in controlling the cell cycle and programmed cell death have been described. Loss of p73 has been demonstrated in neuroblastomas and its involvement in tumorigenesis has been suggested to occur in other neuroectodermal cancers. Since genetic alterations at the tumour suppressor locus 1p36 have been also identified in malignant melanomas, we investigated the expression of p73 in a panel of nine different human melanoma cell lines, 17 melanocytic naevi, 17 primary malignant melanomas and 20 metastases by reverse transcriptase polymerase chain reaction (PCR) and Southern blotting. We observed significant p73 mRNA expression in all the cell lines and tissue specimens except one benign melanocytic naevus and one melanoma metastasis. Sequencing the PCR fragments of nine melanoma cell lines derived from primary tumours and five metastases over the entire p73 DNA binding domain revealed wild-type sequences in all cases. In summary, we conclude that loss of p73 mRNA expression or mutations in the p73 DNA binding domain do not represent common genetic events involved in the pathogenesis of malignant melanomas.
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PMID:Loss of expression or mutations in the p73 tumour suppressor gene are not involved in the pathogenesis of malignant melanomas. 991 12

A novel gene, termed p73 with significant homology to p53, has been identified at 1p36, a chromosomal region which is frequently deleted in malignant melanoma. To determine whether p73 is involved in melanoma development we analyzed 8 benign melanocytic nevi, 17 primary melanomas, 34 melanoma metastases and 9 melanoma cell lines for p73 alterations. Allelic loss at the p73 locus was observed in 2 of 10 cases (20%) and occurred only in metastatic tumors. Mutation analysis of the DNA-binding domain of p73 revealed no somatic mutations in the tumor specimens and melanoma cell lines analyzed, whereas the p53 gene was mutated in 5 of 9 melanoma cell lines. Expression analysis of p73 using semiquantitative RT-PCR demonstrated that p73 is not expressed or at exceedingly low levels in benign melanocytic nevi, primary melanomas and lymph node metastases, but at various levels in melanoma cell lines. Our data indicate that p73 does not play a role as a tumor suppressor in melanoma development.
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PMID:Lack of p73 mutations and late occurrence of p73 allelic deletions in melanoma tissues and cell lines. 1040 74

In the last 2 years, it has become apparent that the p53-family members p53 and p73 play fundamentally different roles in human malignancies. In contrast to p53, many studies on cancer patients failed to detect mutational inactivation of p73 and reported overexpression of wild-type p73 instead. A possible explanation was provided by the recent discovery of N-terminal truncated isoforms of p73 (DeltaTA-p73) that act as dominant-negative inhibitors of wild-type p53 and TA-p73 and result in tumor growth in nude mice. We investigated the role of DeltaTA-p73 in the development and progression of human melanomas, which lack p53 mutations. We analyzed 8 benign melanocytic nevi, 8 primary melanomas and 19 melanoma metastases for alterations of TA-p73 and DeltaTA-p73 expression using isoform-specific real-time RT-PCR. Based on our results, p73Deltaex2 and Deltaex2/3 spliced transcripts derived from the first promoter were significantly up-regulated in melanoma metastases, whereas DeltaN-p73 generated from the second promoter was the predominant isoform in benign nevi. Moreover, increased expression of p73Deltaex2 and p73Deltaex2/3 correlated with high-levels of both TA-p73 and E2F1. Our data suggest a potential function of DeltaTA-p73 splice isoforms in melanoma progression.
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PMID:Alterations of DeltaTA-p 73 splice transcripts during melanoma development and progression. 1461 32

p53 is a transcription factor involved in maintaining genomic integrity by regulating genes involved in cell cycle arrest, DNA repair, and programmed cell death. Various post transcriptional modifications result in activated p53 with varying binding affinity to its targets. The other members of the p53 family (p63, p73) and associated proteins also contribute to the specificity of gene activation resulting in the final cell responses. p53 is commonly mutated in human cancer and is activated by diverse cellular events, including hypoxia. Many sources of genetic diversity, including random or stress-related mutagenesis, affect normal species evolution. The blind subterranean mole rat lives in sealed underground tunnels, subjected to routine hypoxia due to abrupt and sharp changes in O2 supply. We cloned the mole rat's p53 gene and identified two amino acid substitutions in its binding domain, in the same positions that are mutated in cancer. These substitutions lead to increased p53 activation of DNA-repair elements and reduced activation of apoptotic genes. We propose that sequence-specific changes in the mole rat's p53 gene provide an example of how transcription factors that regulate many genes can also account for rapid and broad phenotypic diversity by altering the binding affinity to individual target genes.
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PMID:p53--a key player in tumoral and evolutionary adaptation: a lesson from the Israeli blind subterranean mole rat. 1570 65

The incidence of cutaneous malignant melanoma is increasing worldwide, resulting in the demand for clinically useful prognostic biomarkers, especially for invasive and metastatic disease. We studied the immunohistochemical expression of interleukin-17 (IL-17), IL-23, and p73 in 35 malignant melanomas and compared them with benign melanocytic nevi and Spitz nevi, correlating them with clinical-pathological variables. A higher and statistically significant difference (P<0.05) in the intensity and percentage of stained cells of IL-17 and IL-23 was found in the melanoma group than in ordinary benign nevi that did not correlate with Breslow thickness nor Clark level. Moreover, p73 staining and percentage of stained cells was significantly higher (P<0.05) in all the melanomas studied, with a peculiar cytoplasmatic distribution. Our findings could suggest a possible IL-17, IL-23, and p73 involvement in cutaneous melanomas with a hypothetical impact on melanoma invasiveness.
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PMID:IL-17, IL-23, and p73 expression in cutaneous melanoma: a pilot study. 2579 26