Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10895642 | Biochimica et Biophysica Acta (BBA) - Reviews on Cancer | 2007 | 28 Pages |
Abstract
Ras proteins play a direct causal role in human cancer with activating mutations in Ras occurring in â¼Â 30% of tumours. Ras effectors also contribute to cancer, as mutations occur in Ras effectors, notably B-Raf and PI3-K, and drugs blocking elements of these pathways are in clinical development. In 2000, a new Ras effector was identified, RAS-association domain family 1 (RASSF1), and expression of the RASSF1A isoform of this gene is silenced in tumours by methylation of its promoter. Since methylation is reversible and demethylating agents are currently being used in clinical trials, detection of RASSF1A silencing by promoter hypermethylation has potential clinical uses in cancer diagnosis, prognosis and treatment. RASSF1A belongs to a new family of RAS effectors, of which there are currently 8 members (RASSF1-8). RASSF1-6 each contain a variable N-terminal segment followed by a Ras-association (RA) domain of the Ral-GDS/AF6 type, and a specialised coiled-coil structure known as a SARAH domain extending to the C-terminus. RASSF7-8 contain an N-terminal RA domain and a variable C-terminus. Members of the RASSF family are thought to function as tumour suppressors by regulating the cell cycle and apoptosis. This review will summarise our current knowledge of each member of the RASSF family and in particular what role they play in tumourigenesis, with a special focus on RASSF1A, whose promoter methylation is one of the most frequent alterations found in human tumours.
Keywords
CIMPAPCAP-1PI3-KMST1RSVSV40TSGRTKMSPHNSCCSAVRBP1Lats1RAPLMAP-1NORE1Novel Ras Effector 1JnkTCrMEFTNFαEGFHCCHpoMAPKMAPK/ERK kinaseMethylation-specific PCRCpG island methylator phenotypeSAPK/JNKloss of heterozygosityhippostress-activated protein kinase/c-Jun N-terminal kinaseEBVSCLCtumour necrosis factor alphaApoptosisATMdiacylglycerolRASSFDAGMicrotubuleSARAHSalvadorColorectal cancerNSCLCSmall cell lung cancerNon-small cell lung cancerTumour suppressorepidermal growth factorPhosphatidylinositol 3-kinaseTRAILLOHMethylationMEKmouse embryonic fibroblastRespiratory syncytial virusSimian virus 40human herpes virusHPVactivation protein 1mitogen-activated protein kinaseanaphase-promoting complexCell cycleTumour suppressor geneHead and neck squamous cell carcinomaHepatocellular carcinomaCRCReceptor Tyrosine KinaseT-cell receptor
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Authors
Louise van der Weyden, David J. Adams,