{"title":"Patterns of mutation in cancer cells.","authors":"M Meuth","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The discovery of powerful mutator phenotypes in a subset of colon cancers provides direct support for the hypothesis that destabilization of replication fidelity and repair drive the accumulation of mutations in tumour suppressor or proto-oncogenes. Nevertheless, many important questions remain. The tumour cell lines in which these mutator genes were characterized have many other mutations that may contribute to the mutator phenotype and the characteristic pattern of mutations found in these cells. Thus, mismatch repair deficiency may be necessary for the mutator phenotype, but is it sufficient? Certainly, changes in DNA replication fidelity or cell cycle checkpoint controls may contribute to the mutator phenotype. This question also has important implications for the effect of mismatch repair deficiency on tumour development. Does the mutator phenotype in HNPCC patients arise as a very early event resulting from the loss of the wild type allele or does it arise in later stages only after alterations of cell cycle controls or replication fidelity? Given that eukaryotic cells have numerous homologues of the mismatch repair genes, what are the roles of all these genes? Are these involved in the repair of very specific types of replication errors or do they have other roles in cells? Finally, what mechanisms underlie the accumulation of mutations in other types of tumours? Given the rapid progress made since the isolation of the human homologues of the E coli mismatch repair genes less than 3 years ago, we can look forward to the answers to many of these questions in the near future.</p>","PeriodicalId":77062,"journal":{"name":"Cancer surveys","volume":"28 ","pages":"33-46"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19939378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Epidemiology of sun exposure and skin cancer.","authors":"B K Armstrong, A Kricker","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77062,"journal":{"name":"Cancer surveys","volume":"26 ","pages":"133-53"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19756117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The c-erbB3/HER3 receptor in human cancer.","authors":"W J Gullick","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>c-erbB3 is a receptor for NDF/heregulin that can engage in heterodimerization with other type I receptor tyrosine kinases. Despite very limited kinase activity, it can stimulate responses in heterodimers not evoked by other family members. It is overexpressed frequently in several common solid tumours and thus represents a target for new forms of therapies.</p>","PeriodicalId":77062,"journal":{"name":"Cancer surveys","volume":"27 ","pages":"339-49"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19873471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Control of the ERK MAP kinase cascade by Ras and Raf.","authors":"R Marais, C J Marshall","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Activation of ERKs plays a central part in the control of cell proliferation. In this chapter, we have concentrated on the identification and regulation of the kinases that activate Mek. We have chosen to focus on this area because of the many puzzles associated with it. Key issues for the future are the need to derive methods to determine what contribution each individual activator makes to both the magnitude and duration of Mek activation and understanding the mechanisms of regulation. Furthermore, we have considered the roles of Raf and the other kinases solely as Mek activators; they may well have other substrates including cdc25A (Galaktionov et al, 1995), I kappa B (Li and Sedivy, 1993) and TP53 (Jamal and Ziff, 1995).</p>","PeriodicalId":77062,"journal":{"name":"Cancer surveys","volume":"27 ","pages":"101-25"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19873576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"T cell antigen receptor signal transduction pathways.","authors":"D A Cantrell","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The T cell antigen receptor regulates the activation and growth of T lymphocytes. The initial membrane proximal event triggered by the TCR is activation of protein tyrosine kinases with the resultant phosphorylation of cellular proteins. This biochemical response couples the TCR to a divergent array of signal transduction molecules, including enzymes that regulate lipid metabolism, GTP binding proteins, serine/threonine kinases and adapter molecules. The control of cytokine gene expression is one of the mechanisms that allows the TCR to control immune responses, and this chapter discusses the role of the different TCR signal transduction pathways in linking the TCR to nuclear targets-the transcription factors that control the expression of cytokine genes.</p>","PeriodicalId":77062,"journal":{"name":"Cancer surveys","volume":"27 ","pages":"165-75"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19873579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The role of UVA in the aetiology of non-melanoma skin cancer.","authors":"J M de Laat, F R de Gruijl","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77062,"journal":{"name":"Cancer surveys","volume":"26 ","pages":"173-91"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19756119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Control of ras activation.","authors":"J Downward","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Ras proteins are active when bound to GTP and inactive when bound to GDP: the activation state of Ras proteins is regulated by two families of proteins. GTPase activating proteins (p120GAP, neurofibromin and GAP1) are negative regulators that stimulate hydrolysis of bound GTP to GDP, and guanine nucleotide exchange factors (Sos and Ras-GRF) are positive regulators that stimulate the exchange of GDP bound to Ras for fresh GTP from the cytosol. Ras is activated in response to a wide variety of extracellular stimuli. The principal mechanism used involves formation of complexes of autophosphorylated growth factor receptors with the SH2 and SH3 domain containing adaptor protein GRB2 and the exchange factor Sos. In addition, another adaptor protein, Shc, may bind to GRB2. This causes translocation of Sos to the plasma membrane where Ras is located and hence increases the rate of nucleotide exchange on Ras leading to its activation. The activity of GTPase activating proteins may also be regulated under some circumstances. A number of mechanisms exist to return the activation state of Ras to basal after stimulation.</p>","PeriodicalId":77062,"journal":{"name":"Cancer surveys","volume":"27 ","pages":"87-100"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19873575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The JAK/STAT pathway.","authors":"A F Wilks, A C Oates","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77062,"journal":{"name":"Cancer surveys","volume":"27 ","pages":"139-63"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19873578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Protein tyrosine kinase receptors.","authors":"C H Heldin","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>More than 50 PTK receptors are known to be involved in regulation of cell growth, differentiation, chemotaxis and actin reorganization. PTK receptors can be classified into subfamilies according to their structural features. PTK receptors are activated by ligand induced homo- or heterodimerization, which leads to receptor autophosphorylation on tyrosine residues. In certain receptors, the autophosphorylation regulates the catalytic activity of the kinase. Moreover, autophosphorylated tyrosine residues bind signal transduction molecules with SH2 or PTP domains. Such molecules are activated by the actual binding to the receptors or by phosphorylation on tyrosine residues by the receptor kinase. There are also examples of constitutively active signal transduction molecules that are translocated to act at the cell membrane by binding to autophosphorylated PTK receptors. In this way, specific intracellular signal transduction pathways are initiated. After ligand binding and activation, PTK receptors are internalized and deactivated by dephosphorylation as well as by degradation in the cytoplasm or in the lysosomes.</p>","PeriodicalId":77062,"journal":{"name":"Cancer surveys","volume":"27 ","pages":"7-24"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19874325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}