BACKGROUND _ AIMS: @entity356 develops in the context of parietal cell loss, spasmolytic polypeptide-expressing @entity4648 (SPEM), and intestinal @entity4648 (IM). We investigated whether expression of the activated form of Ras in gastric chief  cells of @entity19 leads to the development of SPEM, as well  as  progression of @entity4648 . METHODS: We studied @entity48500 -CreERT2Tg/+;LSL-K-Ras( @entity4706 )Tg/+ ( @entity48500 - @entity11518 ) @entity19 , which express the active form of @entity11518 in chief cells on @entity440 exposure. We studied @entity48500 -CreERT2Tg/+;LSL- @entity11518 ( @entity4706 )Tg/+;R26RmTmG/+ ( @entity48500 - @entity11518 -mTmG) @entity19 to examine whether chief cells that express active @entity11518 give rise to SPEM and IM. Some @entity19 received intraperitoneal injections of the @entity13438 ( @entity13438 ) inhibitor, @entity17528 , for 14 consecutive days. Gastric tissues were collected and analyzed by immunohistochemistry, immunofluorescence, and quantitative polymerase chain reaction. RESULTS: @entity48500 - @entity11518 @entity19 developed metaplastic glands, which completely replaced normal fundic lineages and progressed to IM within 3-4 months after @entity440 injection. The metaplastic glands expressed markers of SPEM and IM, and were infiltrated by macrophages. Lineage tracing studies confirmed that the @entity4648 developed directly from @entity11518 ( @entity4706 )-induced chief cells. @entity17528 induced persistent regression of SPEM and IM, and re-established normal mucosal cells, which were derived from normal gastric progenitor cells. CONCLUSIONS: Expression of activated Ras in chief cells of @entity48500 - @entity11518 @entity19 led to the full range of metaplastic lineage transitions, including SPEM and IM. Inhibition of Ras signaling by inhibition of @entity13438 might reverse preneoplastic @entity4648 in the stomach.

Expression of Activated Ras in Gastric Chief Cells of XXXX Leads to the Full Spectrum of Metaplastic Lineage Transitions.

@entity48500 :: ('17341(Tax:10090)', 'Gene') :: ['Mist1'] @entity440 :: ('MESH:D013629', 'Chemical') :: ['tamoxifen'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity11518 :: ('16653(Tax:10090)', 'Gene') :: ['KRas', 'Kras'] @entity13438 :: ('17242(Tax:10090)', 'Gene') :: ['MEK', 'Mitogen-activated protein kinase kinase'] @entity4706 :: ('p|SUB|G|12|D', 'ProteinMutation') :: ['G12D'] @entity4648 :: ('MESH:D008679', 'Disease') :: ['metaplasia'] @entity17528 :: ('MESH:C517975', 'Chemical') :: ['Selumetinib', 'selumetinib'] @entity356 :: ('MESH:D013274', 'Disease') :: ['Gastric cancer']
@entity19 :: (10090,Species) :: ['Mice']
