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

Wilms' tumour is an embryonal kidney tumour which exists in an hereditary and sporadic form. Apart from its obvious importance as a model for renal development and differentiation, the tumour has recently been exploited as an example of the action of tumour suppressor genes (or anti-oncogenes). The latter genes are characterised by a somatic loss of genetic information in tumour development, specifically from the short arm of human chromosome 11 in Wilms' tumour. To further study the developmental aspects of the tumour we have established in vitro cell cultures from tumour tissues, which, unlike the majority of Wilms' tumour cell lines, have been genotyped according to their chromosome 11 gene status and their antigen expression patterns, compared to the original normal kidney and tumour tissues. The cell cultures exist both as primary and secondary cultures, and their limited life span in culture has been extended by transfection of SV40 large T antigen. The mechanism of tumour suppression by the Wilms' locus has been explored by producing cell hybrids between the immortalised kidney cells, and an "indicator cell" (HeLa), whose chromosome 11 genotypes have been monitored in vivo and in vitro by restriction fragment length polymorphisms. Non-random patterns of inheritance of the mutant allele have also been investigated, both in tumour tissue and in syndromes, like the Beckwith-Wiedemann Syndrome, which pre-dispose to development of Wilms' tumour (and other embryonal tumours). It is also apparent that allele-specific methylation occurs in Wilms' tumour tissues, probably resulting in changes of gene expression patterns. Significant elevation of transcription of the N-myc oncogene was detected in the blastemal cells of the most malignant Wilms' tumours, whereas a marked decrease in the expression of HLA class I, at both RNA and protein levels was observed in the same cells. Wilm's tumour provides a clear illustration of the requirement for a combination of dominantly and recessively acting genes, in order to produce a malignant embryonal tumour.
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PMID:Molecular and cellular biology of Wilms' tumour. 255 71

Previous reports on possible genomic imprinting of the neuroblastoma tumour suppressor gene on chromosome 1p36 have been conflicting. Here we report on the parental origin of 1p36 alleles lost in 47 neuroblastomas and on a detailed Southern blot analysis of the extent of the 1p deletions in 38 cases. The results are remarkably different for tumours with and without N-myc amplification. In the N-myc single copy tumours we show that the lost 1p36 alleles are of preferential maternal origin (16 of 17 cases) and that the commonly deleted region maps to 1p36.2-3. In contrast, all N-myc amplified neuroblastomas have larger 1p deletions, extending from the telomere to at least 1p35-36.1. These deletions are of random parental origin (18 of 30 maternal LOH). This strongly suggests that different suppressor genes on 1p are inactivated in these two types of neuroblastoma. Deletion of a more proximal suppressor gene is associated with N-myc amplification, while a distal, probably imprinted, suppressor can be deleted in N-myc single copy cases.
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PMID:Evidence for two tumour suppressor loci on chromosomal bands 1p35-36 involved in neuroblastoma: one probably imprinted, another associated with N-myc amplification. 763 1

Neuroblastoma is a childhood neural crest tumour, genetically characterized by frequent deletions of the short arm of chromosome 1 and amplification of N-myc. Here we report the first evidence for a neuroblastoma tumour suppressor locus on 4pter. Cytogenetically we demonstrated rearrangements of 4p in 7 out of 26 evaluable tumours (27%). Subsequent analysis of loss of heterozygosity (LOH) by Southern blotting revealed allelic loss of 4p in 16/82 (19.5%) informative neuroblastomas. Taken together cytogenetic and Southern blot analyses showed loss of 4p in 20/86 neuroblastomas analysed (23%). The common deleted region was bordered by the probe D4S123 and encompassed the distal 34 cM of 4p. We found no evidence for genomic imprinting of the 4p locus as the 4p alleles lost in the tumours were of random maternal and paternal origin. LOH4p was found at all disease stages and in every age group. Furthermore LOH4p was present both in cases with and without LOH1p and amplification of N-myc.
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PMID:Allelic loss of the short arm of chromosome 4 in neuroblastoma suggests a novel tumour suppressor gene locus. 864 6

T-box 2 (TBX2) is a transcription factor involved in mammary development and is known to be overexpressed in a subset of aggressive breast cancers. TBX2 has previously been shown to repress growth control genes such as p14(ARF) and p21(WAF1/cip1). In this study we show that TBX2 drives proliferation in breast cancer cells and this is abrogated after TBX2 small interfering RNA (siRNA) knockdown or after the expression of a dominant-negative TBX2 protein. Using microarray analysis we identified a large cohort of novel TBX2-repressed target genes including the breast tumour suppressor NDRG1 (N-myc downregulated gene 1). We show that TBX2 targets NDRG1 through a previously undescribed mechanism involving the recruitment of early growth response 1 (EGR1). We show EGR1 is required for the ability of TBX2 to repress NDRG1 and drive cell proliferation. We show that TBX2 interacts with EGR1 and that TBX2 requires EGR1 to target the NDRG1 proximal promoter. Abrogation of either TBX2 or EGR1 expression is accompanied by the upregulation of cell senescence and apoptotic markers. NDRG1 can recapitulate these effects when transfected into TBX2-expressing cells. Together, these data identify a novel mechanism for TBX2-driven oncogenesis and highlight the importance of NDRG1 as a growth control gene in breast tissue.
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PMID:T-box 2 represses NDRG1 through an EGR1-dependent mechanism to drive the proliferation of breast cancer cells. 2034 48