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)

MEN1 is a novel tumour suppressor gene involved in the etiology of sporadic endocrine pancreatic tumours. Based on common ontogenetic features of both tissues, we analyzed the role of MEN1 in ductal pancreatic cancer. Wild type MEN1 mRNA expression, but no mutations within the MEN1 coding sequence or MEN1 promoter region were detected in human pancreatic adenocarcinoma tissues and carcinoma cell lines, using sensitive single-strand conformational polymorphism-heteroduplex and sequencing analyses. Thus, human pancreatic cancer does not seem to require inactivation of the MEN1 tumour suppressor pathway.
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PMID:Role of the MEN1 tumour suppressor gene in human ductal pancreatic cancer. 1089 42

Endocrine tumours of the pancreas, anterior pituitary or parathyroids arise either sporadically in the general population, or as a part of inherited syndromes such as multiple endocrine neoplasia type 1 (MEN 1). The mechanisms responsible for the development of sporadic endocrine lesions are not well understood, although loss of heterozygosity (LOH) of the MEN1 locus on chromosome 11q13 and somatic mutation of the MEN1 gene have been frequently associated with the development of MEN 1-type sporadic endocrine lesions. To further investigate the role of the MEN1 gene in sporadic endocrine tumorigenesis, we analysed DNA from 14 primary parathyroid lesions, 8 anterior pituitary tumours and 3 pancreatic tumours for the presence of somatic MEN1 gene mutations and LOH of seven microsatellite markers flanking the MEN1 locus. In addition, we similarly analysed 8 secondary parathyroid lesions which arose in patients with chronic renal failure. None of the patients studied had a family history of MEN 1. Three primary parathyroid lesions and one pancreatic tumour (glucagonoma) were found to have lost one allele at the MEN1 locus. Somatic mutations were identified by SSCP and sequence analysis in one of these parathyroid lesions (P320L) and in the glucagonoma (E179V). These results support previous findings that inactivation of the MEN1 tumour suppressor gene contributes to the development of sporadic MEN 1-type endocrine lesions but is not associated with the development of parathyroid hyperplasia seen in some renal failure patients.
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PMID:Identification of somatic mutations of the MEN1 gene in sporadic endocrine tumours. 1099 46

Pituitary tumours are a common type of intracranial neoplasm and, depending on the cell type of origin, have diverse endocrine and reproductive effects. The developmental biology of the different cell types is understood to result from a sequential activation of a cascade of transcription factors, and mutations in these factors result in various forms of hypopituitarism. Tumours in the pituitary gland arise from activation of dominantly acting oncogenes such as gsp, or from loss of function of a series of tumour suppressor genes such as MEN1. Abnormal patterns of DNA methylation may be implicated in the allelic losses that cause tumour suppressor gene silencing. The different clinically recognized types of pituitary tumour are currently treated by medical therapies such as dopamine and somatostatin agonists, surgery or radiotherapy. However, these treatments are not entirely satisfactory and recent advances in gene therapy may offer valuable new therapeutic opportunities for patients with aggressive tumours that fail to respond to traditional approaches.
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PMID:Pituitary tumours. 1122 62

Loss of heterozygosity (LOH) studies have been used to identify sites harbouring tumour suppressor genes (TSGs) involved in tumour initiation or progression. To further elucidate the genetic mechanisms for follicular and papillary thyroid tumours development, we studied the frequency of LOH in 36 thyroid tumours (21 follicular thyroid adenomas (FAs) and 15 papillary thyroid carcinomas (PTCs)) on 10 specific genomic areas: 3p22, 3p25, 7q21, 7q31, 10q23, 10q25-26, 11q13, 11q23, 13q13 and 17p13.3-13.2 using 20 polymorphic markers. We have selected these areas for two reasons: (a) Even though LOH in thyroid neoplasms has been described in some of these areas, results are controversial, and (b) we have also studied areas described as involved in other epithelial or endocrine tumour types, but not studied up to now in thyroid neoplasms. Two areas showed a high percentage of LOH: 7q31 and 11q23. A 62% LOH was found at 7q31 in the FAs, suggesting, as other authors have proposed, that at least one TSG must be present in the vicinity of the c-met locus. The second area in frequency was at the 11q23 locus, with a 45% LOH in the FAs. This area was studied because it has been described as being involved in the development of epithelial and endocrine cancers. This locus had not been studied before in thyroid neoplasms. This result is interesting because the LOH11CR2A gene is localised at this locus. We suggest that this gene and/or an other TSG nearby may be involved in the progression to FA. In our study, a low percentage of LOH was found in the PTC samples, indicating that TSGs present in the areas we have studied are not significantly involved in their progression. Our data also suggest that TSGs located in areas where no LOH was detected (PTEN, MEN1, Cyclin D1, BRCA2 and RFC3) are not involved or do not have an important role in tumour progression.
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PMID:Screening of selected genomic areas potentially involved in thyroid neoplasms. 1172 Aug 45

The treatment of pituitary tumours strongly depends on their clinical presentation. In general, the treatment aims are reducing tumour volume and/or decreasing hormone hypersecretion. It relies on single or a combination of three different methods: surgery, medication and radiotherapy. The rationale for deciding the treatment are many but include the aggressiveness of the tumour. The aetiologies of sporadic pituitary adenomas are not fully understood. However, several causes have been identified resulting in specific familial phenotypes like multiple endocrine neoplasia type I (MEN1). MEN1 is related to mutations in the MEN1 gene, a tumour suppressor gene localized on chromosome 11q13 and which encodes menin, a 610 amino acid protein. During the last years, an evidence progressively emerged that MEN1-related adenomas were more aggressive and less responsive to therapy than their sporadic counterparts. In this article, we review the differences between sporadic and MEN1-related adenomas and suggest specific ways of treatment and follow-up for MEN1-related tumours.
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PMID:The treatment of sporadic versus MEN1-related pituitary adenomas. 1275 55

Multiple endocrine neoplasia type 1 is an autosomal dominant cancer syndrome affecting primarily parathyroid, enteropancreatic endocrine and pituitary tissues. The inactivating germline and somatic mutations spread throughout the gene and the accompanying loss of the second allele in tumours show that the MEN1 gene is a tumour suppressor. The MEN1-encoded protein, menin, is a novel nuclear protein. Menin binds and alters JunD-, NF-kappaB-, Smad3-mediated transcriptional activation. The mouse Men1 knockout model mimicks the human MEN1 condition contributing to the understanding of tumorigenesis in MEN1.
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PMID:Functional studies of the MEN1 gene. 1275 56

Identification of mutations, which cause genetic diseases can be difficult when the disease is caused by the mutation of a large gene, which contains multiple exons. Detection of these mutations by DNA sequencing can be made more efficient by using mutation detection methods for pre-screening to identify the affected exon and to screen for the presence of already identified mutations in family members. These screening methods include denaturing gradient gel electrophoresis (DGGE), temperature gradient gel electrophoresis (TGGE), single-strand conformation polymorphism, conformation-sensitive gel electrophoresis (CSGE), heteroduplex analysis and denaturing high-performance liquid chromatography (DHPLC). We discuss the advantages and shortcomings of these methods by reviewing the results of studies screening for mutations causing multiple endocrine neoplasia type 1 (MEN 1) syndrome, an autosomal dominant disorder characterized by endocrine tumours of the anterior pituitary gland, parathyroid glands, and pancreas. MEN 1 is caused by mutations of the MEN1 gene, a tumour suppressor gene, which contains one untranslated exon and nine exons. Previous studies have identified more than 400 germline and somatic mutations spreading across all the encoding sequence, and found no mutational "hot spot" or genotype-phenotype correlation. The wide diversity of mutations in the entire coding region of the MEN1 gene makes mutation screening time-consuming and expensive. We conclude that combination of mutation detection methods with DNA sequencing enhances the efficiency of identifying pathogenic mutations. However, it should be considered that experimental determination of the optimal electrophoresis conditions, such as using perpendicular electrophoresis to optimise DGGE or TGGE, is more useful than computerized algorithms to calculate these parameters.
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PMID:Genetic screening methods for the detection of mutations responsible for multiple endocrine neoplasia type 1. 1546 22

Multiple endocrine neoplasia (MEN) types 1 and 2 syndromes are rare hereditary cancer syndromes expressing a variety of endocrine and non-endocrine neoplasias and lesions. The improving of both molecular and clinical genetics knowledge helps health care providers in the whole spectrum of the clinical managements of MEN patients. The MEN1 gene, a tumour suppressor gene, is responsible of MEN1 syndrome, and is probably involved in the regulation of several cell functions, including DNA replication and repair and transcriptional machinery. RET proto-oncogene encodes for a receptor tyrosine kinase protein whose expression is fundamental for appropriate migration, development and differentiation of neuroendocrine cells originating from neural crest. Currently, DNA testing makes possible the early identification of germline mutation in asymptomatic mutant gene carriers in both MEN syndromes. Consequently, the combination of new genetic and diagnostic tools could permit a precocious detection of MEN-associated neoplasms, and in particular the identification of a strong genotype-phenotype correlations in MEN2 syndrome demonstrates an improving outcome and quality of life for affected subjects.
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PMID:Lessons from genes mutated in multiple endocrine neoplasia (MEN) syndromes. 1598 80

The pathogenesis of tumour formation in the anterior pituitary has been intensively studied, but the causative mechanisms involved in pituitary cell transformation and tumourigenesis remain elusive. Most pituitary tumours are sporadic, but some arise as a component of genetic syndromes such as the McCune-Albright syndrome, multiple endocrine neoplasia type 1, Carney complex and, the most recently described, a MEN1-like phenotype (MEN4) and pituitary adenoma predisposition syndromes. Some specific genes have been identified that predispose to pituitary neoplasia (GNAS, MEN1, PRKAR1A, CDKN1B and AIP), but these are rarely involved in the pathogenesis of sporadic tumours. Mutations of tumour suppressor genes or oncogenes, as seen in more common cancers, do not seem to play an important role in the great majority of pituitary adenomas. The pituitary tumour transforming gene (PTTG; securin) was the first transforming gene found to be highly expressed in pituitary tumour cells, and seems to play an important role in the process of oncogenesis. Many tumour suppressor genes, especially those involved in the regulation of the cell cycle, are under-expressed, most often by epigenetic modulation - usually promoter hypermethylation - but the regulator of these co-ordinated series of methylations is also unclear. Cell signalling abnormalities have been identified in pituitary tumours, but their genetic basis is unknown. Both Raf/MEK/ERK and PI3K/Akt/mTOR pathways are over-expressed and/or over-activated in pituitary tumours: these pathways share a common root, including initial activation related to the tyrosine kinase receptor, and we speculate that a change to these receptors or their relationship to membrane matrix-related proteins may be an early event in pituitary tumourigenesis.
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PMID:The pathophysiology of pituitary adenomas. 1994 21

Multiple endocrine neoplasia type I (MEN1) is a rare hereditary cancer syndrome, which is manifested as a variety of endocrine and non-endocrine tumours and lesions caused by specific germline mutations of the MEN1 gene, a tumour suppressor gene. The detection of these germline mutations allows the early identification of affected, possibly still asymptomatic patients. The combined use of genetic and clinical tools for the diagnosis of MEN1-associated tumours substantially improves both the course of the disease and the quality of life of affected patients. This review summarizes the relevant morphological and clinical features of MEN1-associated endocrine and non-endocrine neoplasms and lesions.
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PMID:[Multiple endocrine neoplasia type I]. 2096 Jan 95


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