Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One of the most common cellular gene which negatively regulates the cell cycle, thus functioning as tumour suppressor gene, is the p-53 gene. The presence of this mutated gene has been correlated with, the aggressiveness of several malignant neoplasmas. Expression of the p-53 gene product protein was screened in 55 untreated human germ cell testicular tumours, furthermore a relationship between p-53 expression and clinical resistance was investigated. Using monoclonal antibody and immunoenzyme staining elevated p-53 level could be demonstrated in nuclei of embryonal carcinoma (84%) and seminoma components (56%). Most of the choriocarcinoma cases showed positive staining. Teratomas expressed this antigen negatively or scarcely. In seminomas the highest level of p-53 was stated in stage I. In contrast the opposite tendency could be demonstrated in embryonal carcinomas where p-53 was ++ positive in stage III. Between the high level of p-53 and clinical resistance a converse correlation could be stated because the resistant tumours expressed no or low, the sensitive tumours high level of p-53 protein (P 0.01). These results suggest that elevated p-53 expression could be a prognostic marker of sensitivity in testis cancer.
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PMID:[Correlation between p-53 expression and clinical resistance in testicular cancer]. 872 69

Testicular germ cell tumours (TGCTs) are heterogeneous neoplasms with different histological patterns and malignant potential. The aim of this study was to determine whether the main TGCT subtypes (seminoma, embryonal carcinoma, yolk sac tumour, choriocarcinoma, and mature teratoma) are distinguished by their loss of heterozygosity (LOH) patterns and whether LOH typing can help to distinguish between clonal and multifocal development of different components in mixed TGCTs. In 76 tumours analysed for allelic losses at 25 chromosomal loci, different LOH patterns were found in distinct histological subtypes. A region around D18S543 frequently lost in yolk sac tumours could harbour one or more tumour suppressor genes. In 20 microdissected mixed tumours, losses of identical alleles in different histological components in 11 of 20 cases (over 50 per cent) were found, which is in favour of current histogenetic models of clonal TGCT development. Clonal losses were most often found at D13S317 (6 of 20 tumours). Two classes of allelic losses may therefore occur during TGCT development: clonal losses which are involved in early transformational events and others related to TGCT differentiation along different lines.
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PMID:Loss of heterozygosity, differentiation, and clonality in microdissected male germ cell tumours. 1044 Jul 49

Chk2 is a transducer of DNA damage signals and a tumour suppressor whose germ-line mutations predispose to diverse tumour types. Unlike its downstream targets such as the p53 tumour suppressor, the expression patterns of Chk2 in tissues and tumours remain unknown. As DNA breaks occur commonly during gametogenesis, and p53 is wild-type and overexpressed in testicular cancer, we examined abundance and localisation of the Chk2 protein during normal development of human testes, and at various stages of germ-cell tumour (GCT) pathogenesis. Our results show that Chk2 is abundant in foetal germ cells and adult spermatogonia, yet only weakly expressed or lacking during the meiotic and later stages of spermatogenesis. High levels of Chk2 are detected in the majority of GCTs including all pre-invasive carcinoma-in-situ lesions, contrary to variable expression and even lack of Chk2 in subsets of invasive GCTs and some teratoma structures, respectively. Together with our analyses of cell culture models, these results indicate that downmodulation or lack of Chk2 is not simply attributable to quiescence or differentiation, they suggest a role for Chk2 in mitotic rather than meiotic divisions, support the concept of foetal origin of GCTs, and have implications for protein-based screening for tumour-associated aberrations of Chk2.
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PMID:Chk2 tumour suppressor protein in human spermatogenesis and testicular germ-cell tumours. 1159 95

How cells become malignant has preoccupied scientists for over a century. However, the converse question is also valid: are tumour cells capable of reverting from their malignant state? Askanazy's studies in 1907 indicated that teratoma cells could differentiate into normal somatic tissues and current evidence indicates that some tumour cells have acquired the molecular circuitry that results in the negation of chromosomal instability, translocations, oncogene activation and loss of tumour suppressor genes. Studying these extremely rare events of tumour reversion and deciphering these pathways, which involve SIAH1, presenilin 1, TSAP6 and translationally controlled tumour protein (TCTP), could lead to new avenues in cancer treatment.
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PMID:The molecular programme of tumour reversion: the steps beyond malignant transformation. 1918 95