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)

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.
 ...
PMID:Recessive oncogenes, antioncogenes and tumour suppression. 186 44

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.
 ...
PMID:Genetic alterations within the retinoblastoma locus in colorectal carcinomas. Relation to DNA ploidy pattern studied by flow cytometric analysis. 191 Nov 87

The retinoblastoma susceptibility gene, RB, is the best characterised of the tumour suppressor genes, or 'anti-oncogenes'. Abnormal function of the RB protein is thought to result in loss of an inhibitory effect on cell growth, and thus contribute towards the development of certain human cancers. One group of human cancers of particular interest in relationship to retinoblastoma gene function are the gliomas, which are central nervous system tumours thought to originate from the neuroectoderm, the embryological tissue which also gives rise to retinoblastomas. We have therefore examined a group of benign and malignant gliomas for evidence of structural alterations of the RB gene. Four out of nine (44%) glioblastomas, the most malignant gliomas, showed loss of heterozygosity of a locus within this gene. In addition, one of these hemizygous tumours showed deletion of part of the RB protein-coding region, and this abnormality was also present in cells cultured from the tumour. These findings suggest that RB gene abnormalities may contribute to the development of glioblastomas.
 ...
PMID:Retinoblastoma gene deletions in human glioblastomas. 201 99

The closely related mammalian TGF-betas (TGF-beta 1, TGF-beta 2 and TGF-beta 3) are potent inhibitors of proliferation of many cell types in vitro. TGF-beta 1 has been demonstrated to be growth inhibitory in vivo for epithelial, endothelial, myeloid and lymphoid cells. Utilizing skin keratinocytes as a model system for studying the mechanism of TGF-beta 1-induced growth inhibition, it has been demonstrated that TGF-beta 1 rapidly inhibits transcription of the c-myc gene. Antisense c-myc oligonucleotides inhibit proliferation of keratinocytes as effectively as does TGF-beta 1, indicating that TGF-beta 1 suppression of c-myc expression is an important component of this growth inhibition. Studies utilizing DNA tumour virus transforming gene constructs have shown that the retinoblastoma gene product, pRb, or a related protein, is needed for TGF-beta 1 suppression of c-myc transcription. Thus, TGF-beta 1 may act through a tumour suppressor gene product, pRb, to suppress transcription of a proto-oncogene, c-myc, and subsequently inhibit cell proliferation.
 ...
PMID:Regulation of epithelial proliferation by TGF-beta. 207 Jun 84

Inactivation of the retinoblastoma susceptibility gene (RB-1) has been associated with the aetiology of many types of human cancers, leading to the classification of RB-1 as an anti-oncogene or tumour suppressor gene. Given that the protein product of RB-1 (Rb) has a nuclear localization and DNA-binding activity in vitro, it is possible that Rb regulates transcription of certain genes. The promoter of the c-fos gene might be a target for regulation by Rb, because both v-fos and RB-1 are associated with the induction of osteosarcomas in mice and humans, respectively. Also, fos expression is thought to be required for quiescent cells to enter the cell cycle, making the fos promoter an attractive target for suppressors of cell growth. Here we report that Rb can repress c-fos expression and AP-1 transcriptional activity in both serum-induced and cycling 3T3 cells. We have mapped a cis-acting element in the human c-fos promoter that can confer repression by Rb to a heterologous promoter. We have the termed the cis-acting sequence regulated by Rb the retinoblastoma control element.
 ...
PMID:Negative regulation of human c-fos expression by the retinoblastoma gene product. 211 57

Some observations on cellular senescence are discussed regarding the possibility that the postulated genes, which bring about the DNA synthesis block of senescent fibroblasts, might be similar to those designated as anti-oncogenes or tumour suppressor genes. The latter genes have been defined by tumorogenicity tests of hybrids from fused tumour and normal cells, of which the retinoblastoma (RB) gene is a prototype. Similarities between the two systems are considered, which are consistent with the assumption that senescent growth arrest, like the suppression of tumorogenicity of the hybrids, might be effected by anti-oncogenes via inhibition of cellular oncogenes in their growth signal transduction functions. A link may be provided by the finding of a direct interaction of certain DNA tumour virus oncoproteins with the RB gene product p105-RB, together with observations that the tumour viruses are also able to reinitiate DNA synthesis in growth arrested senescent fibroblasts. The possibility is also discussed that some silent retinoblastoma-like genes might become aberrantly expressed in senescent cells owing to a progressive loss of 5-methyl cytosine residues of DNA.
 ...
PMID:Potential role of anti-oncogenes in aging. 214 70

A novel class of oncogene has been recognised whose loss-of-function results in the expression of the malignant phenotype. Two examples of such genes are the human retinoblastoma predisposition gene (RB1) and the gene encoding the cellular protein p53. These genes are thought to regulate and limit normal proliferation of cells and, as a consequence, can suppress tumorigenicity when introduced into transformed cells. They are hence frequently described as 'tumour suppressor genes'. Both RB1 and p53 gene products are bound by various transforming early proteins encoded by the DNA tumour viruses SV40, adenovirus and human papilloma virus. It is thought that they are thus sequestered and rendered inactive. Thus, a coherent model is emerging whereby inactivation, either by mutation of sequestration, of these tumour suppressor genes may contribute to natural and experimental carcinogenic processes.
 ...
PMID:The nuclear oncoproteins: RB and p53. 215 36

In hereditary cancers the responsible inherited cancer genes are defective (mutated) anti-oncogenes (tumour suppressor genes). This inherited mutation is present in all cells of the organism, and only leads to cancer if in a somatic cell a complete set of specific cancer mutations is accumulated. Since one defective anti-oncogene has been inherited, only three additional somatic cancer mutations are required, according to our previously published view (Anticancer Res 10:1990). The number of de novo arising tumour cells in such a person is thus multiplied by a factor equal to the reverse of the mutant frequency, that is about 10(4)-10(5). This can be observed e.g. in retinoblastoma. Mutations occur in proliferating cells only. Consequently cancer mutations also depend on cell proliferation. If an inherited cancer mutation predisposes to cancer formation in certain organs, then the cancer risk in these organs is enhanced by 10(4)-10(5) times. Tumours in these organs will appear simultaneously if the number of cells and the growth kinetics are similar. This is of course observed in paired organs, like the retina and the female breast. In cancer family syndromes different organs may be affected at the same time. Examples are type I and type II cancer family syndrome and multiple endocrine neoplasia type 1 2a, and 2b. The secondly diagnosed tumours are not caused by metastatic spread. Tumours in two organs will arise at difference times if the number of end cells per organ and the growth kinetics differ. In this case the second tumour is called a second primary malignancy and is not caused by metastatic spread. A good example are the second primary malignancies in hereditary retinoblastoma. The inherited defective anti-oncogene is a recessive gene. This defective inherited gene causes a 10(4)-10(5) fold increase of the normal tumour incidence. This means that nearly always one or more tumours will arise. Evidently, this pattern of inheritance has led to the erroneous conclusion that the genetic abnormality is dominant at the level of the chromosome. The 10(4)-10(5) times enhanced tumour incidence in hereditary cancer is helpful for the clinical recognition of hereditary cancer. That is, hereditary cancer can be recognized not only by family history, but also by early occurrence, the multifocal and bilateral localisation, its occurrence as cancer family syndrome or by second primary malignancies. It is thus recommended to screen patients and families with hereditary cancer for first and second primary tumours. Treatment of patients with hereditary tumours requires extra care to avoid additional cancer mutations.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Hereditary cancer and its clinical implications: a view. 219 May 27

Familial aggregations of defined malignancies are of great importance for determining the genetic factors involved, as has been demonstrated for familial and sporadic retinoblastoma. In nearly all organs, neoplasms occur that are inherited similar to familial retinoblastoma (Rb). For example, more than 5% of all women suffering from breast cancer belong to breast cancer families in which the occurrence of the malignancy suggests an autosomal dominant pattern of inheritance. Familial colon cancer is associated with several well-known autosomal dominantly inherited polyposis syndromes, and also other susceptibilities without obvious clinical features. Site-specific cancers are often accompanied by other malignancies. In addition, there seem to be predispositions to a wider range of different, but well-defined neoplasms: e.g., adenocarcinomatosis of the colon and the endometrium, or the Li-Fraumeni/SBLA syndrome. The latter shows a spectrum of sarcoma, brain tumours, breast cancer, leukaemias, lung and adenocortical cancer. The genes leading to these types of dominantly inherited predispositions appear to be the tentatively so-called tumour suppressor genes, for which the Rb gene serves as a model. It manifests itself recessively on the level of the individual cell, which means both alleles must be deleted or inactivated before a retinoblast develops into a neoplastic cell. Clinical, epidemiological and molecular genetic studies have yet to establish whether the Rb model can be extended to all other forms of dominantly inherited human cancers.
 ...
PMID:Dominant inheritance in human cancer. 219 May 28

Analysis of the age incidence curves for unilateral and bilateral retinoblastoma led Knudson to propose that hereditary tumours may arise by a single event and sporadic tumours by a two stage mutation process. It has been suggested recently that sporadic renal cell carcinoma may arise from a two stage mutation process. We analysed the age incidence curves for symptomatic renal cell carcinoma (n = 26) and cerebellar haemangioblastoma (n = 68) in 109 patients with von Hippel-Lindau (VHL) disease, and compared them to 104 patients with sporadic renal cell carcinoma and 43 patients with sporadic cerebellar haemangioblastoma. The age incidence curves for renal cell carcinoma and cerebellar haemangioblastoma in VHL disease were compatible with a single mutation model, whereas the age incidence curves for sporadic renal cell carcinoma and cerebellar haemangioblastoma suggested a two stage mutation process. These data are compatible with the VHL gene functioning as a recessive tumour suppressor gene. Sporadic cerebellar haemangioblastoma and some renal cell carcinoma may arise from somatic mutations inactivating both alleles at the VHL locus.
 ...
PMID:Statistical analysis of the two stage mutation model in von Hippel-Lindau disease, and in sporadic cerebellar haemangioblastoma and renal cell carcinoma. 235 58


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>