Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/12270
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dc.contributor.authorHayakawa, Yokuen
dc.contributor.authorJin, Guangchunen
dc.contributor.authorWang, Hongshanen
dc.contributor.authorChen, Xiaoweien
dc.contributor.authorWestphalen, Christoph Ben
dc.contributor.authorAsfaha, Samuelen
dc.contributor.authorRenz, Bernhard Wen
dc.contributor.authorAriyama, Hiroshien
dc.contributor.authorDubeykovskaya, Zinaida Aen
dc.contributor.authorTakemoto, Yoshihiroen
dc.contributor.authorLee, Yoomien
dc.contributor.authorMuley, Ashleshaen
dc.contributor.authorTailor, Yagneshen
dc.contributor.authorChen, Duanen
dc.contributor.authorMuthupalani, Sureshkumaren
dc.contributor.authorFox, James Gen
dc.contributor.authorShulkes, Arthuren
dc.contributor.authorWorthley, Daniel Len
dc.contributor.authorTakaishi, Shigeoen
dc.contributor.authorWang, Timothy Cen
dc.date.accessioned2015-05-16T01:55:52Z
dc.date.available2015-05-16T01:55:52Z
dc.date.issued2014-06-20en
dc.identifier.citationGut 2014; 64(4): 544-53en
dc.identifier.govdoc24951258en
dc.identifier.otherPUBMEDen
dc.identifier.urihttp://ahro.austin.org.au/austinjspui/handle/1/12270en
dc.description.abstractProgastrin is the incompletely cleaved precursor of gastrin that is secreted by G-cells in the gastric antrum. Both gastrin and progastrin bind to the CCK2 receptor (Cckbr or CCK2R) expressed on a subset of gastric epithelial cells. Little is known about how gastrin peptides and CCK2R regulate gastric stem cells and carcinogenesis. Interconversion among progenitors in the intestine is documented, but the mechanisms by which this occurs are poorly defined.We generated CCK2R-CreERT mice and performed inducible lineage tracing experiments. CCK2R+ antral cells and Lgr5+ antral stem cells were cultured in a three-dimensional in vitro system. We crossed progastrin-overexpressing mice with Lgr5-GFP-CreERT mice and examined the role of progastrin and CCK2R in Lgr5+ stem cells during MNU-induced carcinogenesis.Through lineage tracing experiments, we found that CCK2R defines antral stem cells at position +4, which overlapped with an Lgr5(neg or low) cell population but was distinct from typical antral Lgr5(high) stem cells. Treatment with progastrin interconverts Lgr5(neg or low) CCK2R+ cells into Lgr5(high) cells, increases CCK2R+ cell numbers and promotes gland fission and carcinogenesis in response to the chemical carcinogen MNU. Pharmacological inhibition or genetic ablation of CCK2R attenuated progastrin-dependent stem cell expansion and carcinogenesis.CCK2R labels +4 antral stem cells that can be activated and expanded by progastrin, thus identifying one hormonal trigger for gastric stem cell interconversion and a potential target for gastric cancer chemoprevention and therapy.en
dc.language.isoenen
dc.subject.otherGASTRIC CANCERen
dc.subject.otherGASTRINen
dc.subject.otherGASTRIN RECEPTORSen
dc.subject.otherINTESTINAL STEM CELLen
dc.titleCCK2R identifies and regulates gastric antral stem cell states and carcinogenesis.en
dc.typeJournal Articleen
dc.identifier.journaltitleGuten
dc.identifier.affiliationDepartment of Surgery, University of Melbourne, Austin Health, Melbourne, Australiaen
dc.identifier.affiliationDivision of Digestive and Liver Disease, Department of Medicine, Columbia University Medical Center, New York, New York, USAen
dc.identifier.affiliationDivision of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, USAen
dc.identifier.affiliationDivision of Digestive and Liver Disease, Department of Medicine, Columbia University Medical Center, New York, New York, USA Department of Internal Medicine III, Klinikum der Universität München, Munich, Germany.en
dc.identifier.affiliationDepartment of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.en
dc.identifier.affiliationDivision of Digestive and Liver Disease, Department of Medicine, Columbia University Medical Center, New York, New York, USA Center for Advanced Medical Innovation, Kyushu University, Fukuoka, Japan.en
dc.identifier.doi10.1136/gutjnl-2014-307190en
dc.description.pages544-53en
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/24951258en
Appears in Collections:Journal articles

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