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dc.contributor.authorBach, Simon P
dc.contributor.authorRenehan, Andrew G
dc.contributor.authorPotten, Christopher S
dc.date.accessioned2009-11-23T12:13:46Z
dc.date.available2009-11-23T12:13:46Z
dc.date.issued2000-03
dc.identifier.citationStem cells: the intestinal stem cell as a paradigm. 2000, 21 (3):469-76 Carcinogenesisen
dc.identifier.issn0143-3334
dc.identifier.pmid10688867
dc.identifier.doi10.1093/carcin/21.3.469
dc.identifier.urihttp://hdl.handle.net/10541/86672
dc.description.abstractStem cell research provides a foundation for therapeutic advancement in oncology, clinical genetics and a diverse array of degenerative disorders. For example, the elucidation of pathways governing proliferative regulation and differentiation within cellular systems will result in medical strategies aimed at the root cause of cancer. At present the characterization of reliable stem cell markers is the immediate aim in this particular field. Over the past 30 years investigators have determined many of the physical and functional properties of stem cells through careful and imaginative experimentation. Intestinal stem cells reside at the crypt base and give rise to all cell types found within the crypt. They readily undergo altruistic apoptosis in response to toxic stimuli although their progeny are hardier and will regain stem cell function to repopulate the tissue compartment, giving rise to the concept of a proliferative hierarchy. Contention exists when deciding whether the full complement of cells within a crypt is derived from either a single or multiple stems. Evidence has also arisen to challenge the long held view that colorectal tumours arise from a single mutated stem cell, as early adenomas from a human XO/XY mosaic contained distinct clones. Mechanisms governing the stem cell cycle and subsequent proliferative activity largely remain obscure. The adenomatous polyposis coli gene product has, however, been shown to promote the degradation of beta-catenin, an enhancer of cell proliferation, thereby downregulating this activity in healthy individuals.
dc.language.isoenen
dc.subjectColorectal Canceren
dc.subjectTumour Suppressor Protein p53en
dc.subject.meshAdenomatous Polyposis Coli
dc.subject.meshAnimals
dc.subject.meshCell Differentiation
dc.subject.meshCell Division
dc.subject.meshColorectal Neoplasms
dc.subject.meshCyclin-Dependent Kinase Inhibitor p21
dc.subject.meshCyclins
dc.subject.meshCyclooxygenase 2
dc.subject.meshGlucagon-Like Peptides
dc.subject.meshHumans
dc.subject.meshIntestinal Mucosa
dc.subject.meshIntestines
dc.subject.meshIsoenzymes
dc.subject.meshMembrane Proteins
dc.subject.meshNeoplasms
dc.subject.meshPeptides
dc.subject.meshProstaglandin-Endoperoxide Synthases
dc.subject.meshProto-Oncogene Proteins c-bcl-2
dc.subject.meshSignal Transduction
dc.subject.meshStem Cells
dc.subject.meshTransforming Growth Factor beta
dc.subject.meshTumor Suppressor Protein p53
dc.titleStem cells: the intestinal stem cell as a paradigm.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Epithelial Biology, Paterson Institute for Cancer Research and Department of Surgery, Christie Hospital NHS Trust, Wilmslow Road, Manchester, UK.en
dc.identifier.journalCarcinogenesisen
html.description.abstractStem cell research provides a foundation for therapeutic advancement in oncology, clinical genetics and a diverse array of degenerative disorders. For example, the elucidation of pathways governing proliferative regulation and differentiation within cellular systems will result in medical strategies aimed at the root cause of cancer. At present the characterization of reliable stem cell markers is the immediate aim in this particular field. Over the past 30 years investigators have determined many of the physical and functional properties of stem cells through careful and imaginative experimentation. Intestinal stem cells reside at the crypt base and give rise to all cell types found within the crypt. They readily undergo altruistic apoptosis in response to toxic stimuli although their progeny are hardier and will regain stem cell function to repopulate the tissue compartment, giving rise to the concept of a proliferative hierarchy. Contention exists when deciding whether the full complement of cells within a crypt is derived from either a single or multiple stems. Evidence has also arisen to challenge the long held view that colorectal tumours arise from a single mutated stem cell, as early adenomas from a human XO/XY mosaic contained distinct clones. Mechanisms governing the stem cell cycle and subsequent proliferative activity largely remain obscure. The adenomatous polyposis coli gene product has, however, been shown to promote the degradation of beta-catenin, an enhancer of cell proliferation, thereby downregulating this activity in healthy individuals.


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