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Genomes and Genes | Owen SansomSummaryAffiliation: University of Glasgow Country: UK Publications
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Publications
C-Myc is a critical mediator of the phenotypes of Apc loss in the intestineJulie A Wilkins
Beatson Insitute of Cancer Research, Garscube Estate, Swithback Road, Glasgow, United Kingdom
Cancer Res 68:4963-6. 2008..The importance of investigating Apc and C-Myc gene function in the correct tissue context is also discussed...
B-catenin deficiency, but not Myc deletion, suppresses the immediate phenotypes of APC loss in the liverKaren R Reed
School of Biosciences, University of Cardiff, Cardiff CF10 3AX, United Kingdom
Proc Natl Acad Sci U S A 105:18919-23. 2008....- The pro-apoptotic K-Ras 4A proto-oncoprotein does not affect tumorigenesis in the ApcMin/+ mouse small intestineCharles E Patek
Sir Alastair Currie Cancer Research UK Laboratories, Molecular Medicine Centre, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK
BMC Gastroenterol 8:24. 2008..By this means tumorigenesis in the small intestine was compared between ApcMin/+, K-ras+/+ and ApcMin/+, K-rastmDelta4A/tmDelta4A mice that can, and cannot, express the K-ras 4A proto-oncoprotein respectively... - A limited role for p53 in modulating the immediate phenotype of Apc loss in the intestineKaren R Reed
Cardiff School of Biosciences, Cardiff University, Cardiff, CF10 3US, UK
BMC Cancer 8:162. 2008..Although p53-dependent regulation of Wnt signalling activity is known to occur, the importance of these regulatory mechanisms during the early stages of intestinal neoplasia has not been demonstrated... - PPARdelta status and mismatch repair mediated neoplasia in the mouse intestineKaren R Reed
Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF103US, UK
BMC Cancer 6:113. 2006..To further investigate the PPARdelta dependency of intestinal tumourigenesis, we have analysed the consequences of PPARdelta deficiency upon intestinal neoplasia occurring in mice with impaired mismatch DNA repair... 
Tissue-specific tumour suppression by APCOwen Sansom
Beaton Institute of Cancer Research, Glasgow, Scotland, UK
Adv Exp Med Biol 656:107-18. 2009....- Efficient Wnt mediated intestinal hyperproliferation requires the cyclin D2-CDK4/6 complexKevin Myant
The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK
Cell Div 6:3. 2011..It also argues that inhibition of this complex may be an effective chemopreventative strategy in CRC... - Cyclin D1 is not an immediate target of beta-catenin following Apc loss in the intestineOwen J Sansom
School of Biosciences, University of Cardiff, Museum P O Box 911, Cardiff CF103US, Wales, United Kingdom
J Biol Chem 280:28463-7. 2005..Taken together, this argues that cyclin D1 up-regulation in intestinal neoplasia is important for tumor progression rather than initiation... - Loss of Apc allows phenotypic manifestation of the transforming properties of an endogenous K-ras oncogene in vivoOwen J Sansom
Beatson Institute for Cancer Research, Glasgow G61 1BD, United Kingdom
Proc Natl Acad Sci U S A 103:14122-7. 2006..These data imply a window of opportunity for anti-K-ras therapies after tumor initiation in preventing tumor growth and invasion... - Myc deletion rescues Apc deficiency in the small intestineOwen J Sansom
The Beatson Institute, Garscube Estate, Glasgow G61 1BD, UK
Nature 446:676-9. 2007..Array analysis revealed that Myc is required for the majority of Wnt target gene activation following Apc loss. These data establish Myc as the critical mediator of the early stages of neoplasia following Apc loss... - PPARdelta status and Apc-mediated tumourigenesis in the mouse intestineKaren R Reed
Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF103US, UK
Oncogene 23:8992-6. 2004..Our data suggest that PPARdelta is not directly regulated by beta-catenin, and that inhibition of PPARdelta activity is unlikely to be an appropriate strategy for the chemoprevention or chemotherapy of intestinal malignancies... - Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migrationOwen J Sansom
School of Biosciences, University of Cardiff, Cardiff CF10 3US, Wales
Genes Dev 18:1385-90. 2004..Critically, for the first time we confirm a series of Wnt target molecules in an in vivo setting and also identify a series of new candidate targets within the same setting... - Loss of APC induces polyploidy as a result of a combination of defects in mitosis and apoptosisDina Dikovskaya
Division of Cell and Developmental Biology, University of Dundee, Dundee DD1 5EH, Scotland, UK
J Cell Biol 176:183-95. 2007..We suggest that these defects amplify each other to increase the incidence of tetra- and polyploidy in early stages of tumorigenesis... - Cyclin D2-cyclin-dependent kinase 4/6 is required for efficient proliferation and tumorigenesis following Apc lossAlicia M Cole
Beatson Institute of Cancer Research, Glasgow, United Kingdom School of Biosciences, Cardiff, United Kingdom
Cancer Res 70:8149-58. 2010.... - APC as a master regulator of intestinal homeostasis and transformation: from flies to vertebratesJulia Cordero
The Beatson Institute for Cancer Research, Glasgow, UK
Cell Cycle 8:2926-31. 2009..Here we discuss the similarities and differences between these model organisms in regards to the role of Wnt signaling and APC in intestinal homeostasis and transformation... - Spatial regulation of RhoA activity during pancreatic cancer cell invasion driven by mutant p53Paul Timpson
The Beatson Institute for Cancer Research, Garscube Estate, Glasgow, United Kingdom
Cancer Res 71:747-57. 2011.... - p53 mutation and loss have different effects on tumourigenesis in a novel mouse model of pleomorphic rhabdomyosarcomaBrendan Doyle
Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK
J Pathol 222:129-37. 2010..These data demonstrate that mutant p53 can co-operate with activated, mutant KRas to influence tumourigenesis and metastatic potential, over and above simple loss of normal protein function... - Deficiency of Mbd2 suppresses intestinal tumorigenesisOwen J Sansom
Cardiff School of Biosciences, Cardiff University, Cardiff, Wales, UK
Nat Genet 34:145-7. 2003..As Mbd2-deficient mice are viable and fertile, their resistance to intestinal cancer may be of therapeutic relevance... - Deficiency of SPARC suppresses intestinal tumorigenesis in APCMin/+ miceOwen J Sansom
Beatson Institute of Cancer Research, Glasgow, Scotland, UK
Gut 56:1410-4. 2007..More recently, it has been shown to be upregulated in human gastric and colorectal cancer. We therefore wished to address the functional importance of SPARC upregulation to intestinal tumorigenesis in vivo... - Advances in mouse models of prostate cancerImran Ahmad
The Beatson Institute for Cancer Research, Glasgow, UK
Expert Rev Mol Med 10:e16. 2008..Compound mutational models will also develop further, with double and triple knock-in or knockout systems adding to our knowledge of the interaction between different signalling cascades... - Focal adhesion kinase is required for intestinal regeneration and tumorigenesis downstream of Wnt/c-Myc signalingGabrielle H Ashton
The Beatson Institute for Cancer Research, Glasgow, UK
Dev Cell 19:259-69. 2010..Importantly, this work suggests that FAK inhibitors may suppress tumorigenesis in patients at high risk of developing colorectal cancer... - Dasatinib inhibits the development of metastases in a mouse model of pancreatic ductal adenocarcinomaJennifer P Morton
Beatson Institute for Cancer Research, Glasgow, United Kingdom
Gastroenterology 139:292-303. 2010..The aim of this study was to assess the importance of Src in human PDAC and to use a genetically engineered mouse model of PDAC to determine the effects of dasatinib on PDAC progression... - LKB1 haploinsufficiency cooperates with Kras to promote pancreatic cancer through suppression of p21-dependent growth arrestJennifer P Morton
Beatson Institute for Cancer Research, Garscube Estate, Glasgow, UK
Gastroenterology 139:586-97, 597.e1-6. 2010..In this study, we aimed to investigate the impact of LKB1 down-regulation for pancreatic cancer in mouse and human and to elucidate the mechanism by which Lkb1 deregulation contributes to this disease... - Mutant p53 drives invasion by promoting integrin recyclingPatricia A J Muller
The Beatson Institute for Cancer Research, Switchback Road, Bearsden, Glasgow G61 1BD, UK
Cell 139:1327-41. 2009..These findings open the possibility that blocking alpha5/beta1-integrin and/or the EGF receptor will have therapeutic benefit in mutant p53-expressing cancers... - Apoptosis and mutation in the murine small intestine: loss of Mlh1- and Pms2-dependent apoptosis leads to increased mutation in vivoOwen J Sansom
School of Biosciences, University of Cardiff, Museum Avenue, P O Box 911, Cardiff, Wales CF10 3US, UK
DNA Repair (Amst) 2:1029-39. 2003..However, when MMR does mediate apoptosis, perturbation of this response leads to long-term persistence of mutant cells in vivo... - Identification of potential biomarkers for measuring inhibition of Src kinase activity in colon cancer cells following treatment with dasatinibAlan Serrels
The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow, G61 1BD, United Kingdom
Mol Cancer Ther 5:3014-22. 2006..Thus, peripheral blood mononuclear cells may provide a useful surrogate tissue for biomarker studies with dasatinib using inhibition of Src Tyr(419) and paxillin Tyr(118) phosphorylation as read-outs of Src activity... - Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancerJennifer P Morton
Beatson Institute for Cancer Research, Glasgow G61 1BD, United Kingdom
Proc Natl Acad Sci U S A 107:246-51. 2010.... - MBD4 deficiency does not increase mutation or accelerate tumorigenesis in mice lacking MMROwen J Sansom
School of Biosciences, University of Cardiff, Museum Avenue, PO Box 911, Cardiff CF10 3US, UK
Oncogene 23:5693-6. 2004..Taken together, these findings show that nullizygosity or heterozygosity for Mbd4 does not affect MMR-dependent tumorigenesis... - The ability to engage enterocyte apoptosis does not predict long-term crypt survival in p53 and Msh2 deficient miceOwen J Sansom
Cardiff School of Biosciences, University of Cardiff, CF10 3US, UK
Oncogene 21:5934-9. 2002..We conclude that loss of either p53 or Msh2 dependent apoptosis does not predict long-term crypt survival in vivo, however genetic status clearly can modulate survival for some agents such as cisplatin... - Brca2 deficiency in the murine small intestine sensitizes to p53-dependent apoptosis and leads to the spontaneous deletion of stem cellsTrevor Hay
School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3US, UK
Oncogene 24:3842-6. 2005..Furthermore, we show that Brca2 deficiency results in the spontaneous deletion of stem cells, thereby protecting the small intestine against tumorigenesis... - Apc deficiency predisposes to renal carcinoma in the mouseOwen J Sansom
Cardiff School of Biosciences, Cardiff University, Wales CF10 3US, UK
Oncogene 24:8205-10. 2005..Compared to other murine models of kidney neoplasia, this represents particularly rapid onset of disease, and so implicates an important role for Apc in suppressing renal carcinoma... - Rapid loss of intestinal crypts upon conditional deletion of the Wnt/Tcf-4 target gene c-MycVanesa Muncan
Hubrecht Laboratory, Nederlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
Mol Cell Biol 26:8418-26. 2006..c-Myc appears essential for crypt progenitor cells to provide the necessary biosynthetic capacity to successfully progress through the cell cycle... - Aspirin activates the NF-kappaB signalling pathway and induces apoptosis in intestinal neoplasia in two in vivo models of human colorectal cancerLesley A Stark
Division of Oncology, School of Clinical and Molecular Medicine, University of Edinburgh, Colon Cancer Genetics Group, MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK
Carcinogenesis 28:968-76. 2007..These data have considerable relevance to cancer prevention and therapy... - Mutations in Apc and p53 synergize to promote mammary neoplasiaValerie Meniel
School of Biological Sciences, Cardiff University, Cardiff, United Kingdom
Cancer Res 65:410-6. 2005..We therefore show clear synergy between these two mutations in mammary gland neoplasia and present data to suggest that at least one mechanism for this acceleration is the p53-dependent loss of Apc-deficient cells... - Efficient deletion of normal Brca2-deficient intestinal epithelium by poly(ADP-ribose) polymerase inhibition models potential prophylactic therapyTrevor Hay
School of Bioscience, Cardiff University, Cardiff, United Kingdom
Cancer Res 65:10145-8. 2005.... - Inactivation of Apc perturbs mammary development, but only directly results in acanthoma in the context of Tcf-1 deficiencyRonald C J Gallagher
Department of Biomedical Sciences, University of Edinburgh, Medical School, Teviot Place, Edinburgh EH8 9AG, UK
Oncogene 21:6446-57. 2002..However, additional deficiency of Tcf-1 completely blocks normal mammary development and results in acanthoma... - Analyzing tumor suppressor activities in the murine small intestineAlan R Clarke
Cardiff School of Biosciences, Cardiff University, Cardiff, CF10 3US, UK
Oncol Res 13:333-7. 2003..Finally, we have analyzed mice mutant for Mbd4 and show that this gene functions in vivo as a tumor suppressor... - Deficiency of Mbd2 attenuates Wnt signalingToby J Phesse
Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3US, United Kingdom
Mol Cell Biol 28:6094-103. 2008..Furthermore, we show that Lect2 is capable of functioning as a Wnt pathway repressor. These results therefore provide a mechanistic basis for the epigenetic control of adenoma formation mediated through Mbd2... - Enhanced CpG mutability and tumorigenesis in MBD4-deficient miceCatherine B Millar
Wellcome Trust Centre for Cell Biology, The King s Buildings, Edinburgh University, Edinburgh EH9 3JR, UK
Science 297:403-5. 2002..On a cancer-susceptible Apc(Min/+) background, Mbd4-/- mice showed accelerated tumor formation with CpG --> TpG mutations in the Apc gene. Thus MBD4 suppresses CpG mutability and tumorigenesis in vivo... - Inducible Cre-mediated control of gene expression in the murine gastrointestinal tract: effect of loss of beta-cateninHeather Ireland
Department of Oncology, Cancer Research UK, Cambridge Institute of Medical Research, Wellcome Trust MRC Building, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2XY, UK
Gastroenterology 126:1236-46. 2004.... - Heterozygosity for p53 promotes microsatellite instability and tumorigenesis on a Msh2 deficient backgroundNeil J Toft
Department of Pathology, University Medical School, Teviot Place, Edinburgh EH8 9AG, UK
Oncogene 21:6299-306. 2002..Our results therefore demonstrate a dose sensitive role for p53 in the maintenance of genomic integrity at the nucleotide level... - Mechanisms of disease: methyl-binding domain proteins as potential therapeutic targets in cancerOwen J Sansom
Cardiff School of Biosciences, Cardiff University, Cardiff, UK
Nat Clin Pract Oncol 4:305-15. 2007..We review the recent work addressing this possibility, and discuss several of the MBD proteins as potentially excellent novel therapeutic targets... - Mutationally activated K-ras 4A and 4B both mediate lung carcinogenesisCharles E Patek
Sir Alastair Currie Cancer Research UK Laboratories, Molecular Medicine Centre, The University of Edinburgh, Western General Hospital, Edinburgh, UK
Exp Cell Res 314:1105-14. 2008....