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)

As yet, few molecular markers are available that are likely to be useful in predicting the metastatic potential of prostate cancer cancer cells. The need for such "progression markers" is indicated by the expectation that more localized cancers (ie stage A-2, B-1,2) will be clinically diagnosed in the near future, owing to improvements in diagnostic techniques (eg transrectal ultrasound) and the screening of population groups at risk (males over 50 years old). Few model systems are available for such studies. Animal models are unsuitable for the isolation of monoclonal antibodies that detect epitopes associated with the progression of prostate cancer. Since few cell lines are available, an approach using primary cancer tissue should be undertaken. For the differential hybridization approach described here, the choice of species presents no difficulty, since many DNA sequences are conserved between species. However, no model system fully represents the human situation. Hence, differential hybridization studies using primary prostate cancer tissue need to be considered. Moreover, the group of genes/proteins with potential relevance for cancer progression (eg oncogenes, tumour suppressor genes, genes encoding cell adhesion molecules or growth factors) has not been studied extensively in prostate cancer. Because of the intrinsic heterogeneity of prostate tumours, the use of pathologically defined tissue sections is imperative for a reliable study. This could be achieved either by in situ techniques (whereby tissue morphology is conserved) or by step sectioning. The difficulties associated with the small amount of material obtained from such sections can be overcome by the use of techniques based on the polymerase chain reaction. Taking these considerations into account, a systematic screening of prostate cancer with probes representing the above mentioned genes should be undertaken.
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PMID:Molecular methods for predicting the metastatic potential of prostate cancer. 172 88

The tumour suppressor gene p53 has been found to be mutated or inactivated at high frequency in several common human tumours. We have examined a series of exocrine pancreatic carcinomas for over-expression of mutant forms of p53 by immunohistochemistry with a panel of specific antibodies. We found immunodetectable p53 in 13 of 22 (60%) frozen pancreatic cancers and seven of 13 pancreatic cell lines. One of the antibodies, CM1, recognises p53 in formalin-fixed, paraffin-embedded archival material and using this reagent we found immunodetectable p53 in 28 of 124 (23%) pancreatic cancers. We have successfully demonstrated the presence of point mutations by direct sequencing of genomic DNA extracted from archival tissue showing CM1 immunoreactivity. We conclude that p53 activation is an important event in human pancreatic tumorigenesis and that the CM1 antibody can detect a proportion of cases of overexpression of mutant p53 in archival pathological material.
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PMID:Abnormalities of the p53 tumour suppressor gene in human pancreatic cancer. 176 70

Recent studies have suggested the existence of a tumor suppressor gene located at chromosome region 5q21. DNA probes from this region were used to study a panel of sporadic colorectal carcinomas. One of these probes, cosmid 5.71, detected a somatically rearranged restriction fragment in the DNA from a single tumor. Further analysis of the 5.71 cosmid revealed two regions that were highly conserved in rodent DNA. These sequences were used to identify a gene, MCC (mutated in colorectal cancer), which encodes an 829-amino acid protein with a short region of similarity to the G protein-coupled m3 muscarinic acetylcholine receptor. The rearrangement in the tumor disrupted the coding region of the MCC gene. Moreover, two colorectal tumors were found with somatically acquired point mutations in MCC that resulted in amino acid substitutions. MCC is thus a candidate for the putative colorectal tumor suppressor gene located at 5q21. Further studies will be required to determine whether the gene is mutated in other sporadic tumors or in the germ line of patients with an inherited predisposition to colonic tumorigenesis.
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PMID:Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers. 184 68

Oncogenesis results from an accumulation of genetic mutations in a single cell. Mutations may result in the cell acquiring new functions or losing specific functions required for normal growth control. Evidence for the latter may be adduced from the results of fusing tumour and normal cells to form somatic cell hybrids, and from studies of allele loss in a number of human tumours. The locations the critical genes have been discerned in some cancer predisposition syndromes either by observations of consistent cytogenetic abnormalities, or by genetic linkage studies, or both. Genes whose inactivation is important in the genesis of retinoblastoma, Wilms' tumour and colorectal cancer have been identified and cloned. Their normal functions include control of transcription and cell-cell interactions. In the case of retinoblastoma, the interaction between the normal gene product and that of the transforming genes of a number of oncogenic DNA viruses has been delineated. Identification of 'tumour suppressor' genes has not only improved understanding of the process of oncogenesis, but may also aid in the presymptomatic detection of mutant gene carriers.
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PMID:Recessive oncogenes, antioncogenes and tumour suppression. 186 44

Cancer can be considered a genetic disorder of somatic cells. Strong evidence comes from several areas: (1) chromosomal analysis reveals cancer cells have abnormal karyotypes; (2) some inherited syndromes are associated with an increased risk of cancer and for others, cancer itself occurs as an inherited trait; (3) cells can become malignant by a variety of agents that damage DNA, and (4) some types of viruses can induce tumours. One common thread has been the normal cellular sequences transduced by viruses and mutated to become oncogenic (oncogenes) are the same sequences to become activated by nonviral mechanisms. These oncogenes appear involved in cell proliferation and/or differentiation and their products apparently function in the signal transduction pathway from the cell exterior to the nucleus. In addition, evidence from familial studies indicate mutations associated with gene inactivation or loss of function are also important in the aetiology of tumour formation. These genes, termed tumour suppressor genes, seem to be involved in the negative control of cellular proliferation. Cancer is a multistep process and it is now becoming clear that the different stages involve genetic alterations in both oncogenes and tumour suppressor genes.
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PMID:Genes and cancer. 186 49

Alterations within the retinoblastoma (Rb) gene, as detected by the VNTR probe p68RS2.0, and flow cytometric DNA pattern have been analysed in 255 colorectal carcinomas. A total of 35.3% of the tumours had alterations within the Rb gene. Amplification of one allele was demonstrated in 29.5% of the tumours, and loss of heterozygosity was found in 11.5%. No association was found between amplification within the Rb gene and clinicopathological characteristics of the patients. The high frequency of alterations demonstrated within the Rb gene, suggests that this gene is involved in colorectal carcinogenesis with amplification as by far the most abundant genetic alteration. This may imply that the Rb gene has an oncogene-like function in colorectal carcinomas, rather than acting as a tumour suppressor gene. Sixty-three per cent of the carcinomas were DNA aneuploid, and a significant association was demonstrated between amplification within the Rb gene and DNA aneuploidy (P less than 0.01). Two other chromosome loci were analysed, on chromosome 1p (probe pYNZ2) and on chromosome 2p (probe pYNH24), respectively. On chromosome 1p, heterozygous loss was found in 22.2% of the tumours, indicating an involvement of this chromosome in a subset of colorectal carcinomas.
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PMID:Genetic alterations within the retinoblastoma locus in colorectal carcinomas. Relation to DNA ploidy pattern studied by flow cytometric analysis. 191 Nov 87

The p53 gene has been implicated as a tumour suppressor, with mutations occurring in many carcinomas, such as colon, breast and lung. We have sequenced exons 5, 7 and 8 containing conserved gene regions in the only available differentiated thyroid follicular carcinoma cell line and found a mutation at position 273, Arg----His, with no normal allele present. The same mutation was also present in DNA from the tumour of origin. However immunohistochemical analysis of 129 human thyroid tumours using a panel of p53 antibodies was unequivocally negative. Southern blotting in 20 cases failed to demonstrate any deletion or rearrangement, and direct genomic sequencing of 20 carcinomas showed normal DNA sequence for exons 5, 7 and 8. Thus p53 abnormalities may not be important in human thyroid carcinogenesis, in contrast to colon, breast and lung. However, the FTC 133 cell line was only established after 132 unsuccessful attempts with other differentiated thyroid follicular tumours. Since this line and the corresponding tumour of origin have a p53 mutation, we propose that p53 mutation may confer on thyroid follicular tumour cells the ability to grow in culture. This has potential applications for the future development of thyroid carcinoma cell lines.
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PMID:Mutation of the p53 gene in a differentiated human thyroid carcinoma cell line, but not in primary thyroid tumours. 192 34

Human papillomaviruses (HPVs) appear to play a role in the etiology of the vast majority of virus-associated human malignancies. Studies of viral gene expression in carcinomas suggest the importance of two HPV encoded proteins, E6 and E7, in malignant development and these proteins have been shown to encode transforming and immortalising activities. The two proteins show some functional resemblance to the transforming proteins of other small DNA tumour viruses such as adenovirus and SV40. Recent evidence suggests that one important function of these virus-encoded proteins is binding the products of the cellular tumour suppressor genes RB and p53, revealing an exciting link between oncogenes and anti-oncogenes.
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PMID:Human papillomavirus oncoproteins. 196 93

The growth of normal breast epithelial cells is regulated by a complex interacting system of polypeptide factors and by steroid hormones. The cells respond to these factors through receptors which generate mitogenic and other intracellular signals. These second messengers provoke complex responses which may ultimately result in DNA replication and cell division. A comparison of normal cells and tumour cells, either in culture or from primary tumour biopsies, has revealed differences in growth factor and growth factor receptor expression. Such changes may represent aspects of the process of malignant transformation. In addition some evidence suggests that changes in second messenger systems may also occur. Finally several changes in nuclear oncogenes have been observed in breast cancers. It has been proposed that changes in the nuclear oncogenes, perhaps involving the loss of function of tumour suppressor genes, may allow cells to enter the cell cycle. Changes in growth factors, their receptors or intracellular second messenger systems may stimulate unregulated growth. The combination of these events provide a model for the process of carcinogenesis.
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PMID:Growth factors and oncogenes in breast cancer. 196 56

The DNA of paired tumour and blood leucocyte samples from a large series of breast cancer patients was analysed to map regions of loss of heterozygosity on chromosome 17. The high frequency of loss of heterozygosity on 17p was confirmed, and a third of informative tumours had also lost an allele at the long arm locus THH59. On the short arm two distinct regions of loss of heterozygosity were identified, in bands p13-3 and p13-1. The latter probably involves the structural gene p53, which has been implicated as an oncogene or as a tumour suppressor in various human cancers. 17p 13-3, however, showed a significantly higher frequency of loss of heterozygosity, and there was no correlation between allele losses at the two sites. Nevertheless, loss of heterozygosity at 17p 13-3 is associated with overexpression of p53 mRNA, suggesting the existence of a gene some 20 megabases telomeric of p53 that regulates its expression. Lesions of this regulatory gene seem to be involved in the majority of breast cancers.
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PMID:Evidence implicating at least two genes on chromosome 17p in breast carcinogenesis. 197 43


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